Browsing by Subject "WEIGHT-LOSS"

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  • Mardinoglu, Adil; Wu, Hao; Bjornson, Elias; Zhang, Cheng; Hakkarainen, Antti; Räsänen, Sari M.; Lee, Sunjae; Mancina, Rosellina M.; Bergentall, Mattias; Pietiläinen, Kirsi H.; Söderlund, Sanni; Matikainen, Niina; Stahlman, Marcus; Bergh, Per-Olof; Adiels, Martin; Piening, Brian D.; Graner, Marit; Lundbom, Nina; Williams, Kevin J.; Romeo, Stefano; Nielsen, Jens; Snyder, Michael; Uhlen, Mathias; Bergstrom, Goran; Perkins, Rosie; Marschall, Hanns-Ulrich; Backhed, Fredrik; Taskinen, Marja-Riitta; Boren, Jan (2018)
    A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.
  • Mikkola, Tuija M; Salonen, Minna K; Kajantie, Eero; Kautiainen, Hannu; Eriksson, Johan G (2020)
    Circulating amino acids are potential markers of body composition. Previous studies are mainly limited to middle age and focus on either fat or lean mass, thereby ignoring overall body composition. We investigated the associations of fat and lean body mass with circulating amino acids in older men and women. We studied 594 women and 476 men from the Helsinki Birth Cohort Study (age 62–74 years). Bioelectrical impedance analysis was used to indicate two main body compartments by fat (fat mass/height2) and lean mass indices (lean mass/height2), dichotomized based on sex-specific medians. Eight serum amino acids were quantified using nuclear magnetic resonance spectroscopy. General linear models were adjusted for age, smoking, and fasting glucose. Higher lean mass index (LMI) was associated with higher concentrations of branched-chain amino acids in both sexes (p ≤ .001). In men, LMI was also positively associated with tyrosine (p = .006) and inversely with glycine (p < .001). Higher fat mass index was associated with higher concentrations of all branched-chain amino acids, aromatic amino acids (phenylalanine and tyrosine), and alanine in both sexes (p ≤ .008). Associations between body composition and amino acids are largely similar in older men and women. The associations are largely similar to those previously observed in younger adults.
  • Jolle, Anne; Asvold, Bjorn Olav; Holmen, Jostein; Carlsen, Sven Magnus; Tuomilehto, Jaakko; Bjorngaard, Johan Hakon; Midthjell, Kristian (2018)
    Objective Among individuals at high risk for diabetes identified through a population survey, we performed an intervention study with basic lifestyle advice aiming to prevent diabetes. Research design and methods Among 50 806 participants in the HUNT3 Survey (2006-2008), 5297 individuals with Finnish Diabetes Risc Score (FINDRISC >= 15 were invited to an oral glucose tolerance test (OGTT) and an education session with lifestyle advice, and 2634 (49.7%) attended. Among them, 2380 people without diabetes were included in the prevention study with repeated examinations and education sessions after 6, 12, and 24 months. We examined participation, diabetes incidence, glycemia, and adiposity during follow-up. Results Of 2380 participants, 1212 (50.9%) participated in >= 3 of the four examinations. Diabetes was detected in 3.5%, 3.1%, and 4.0% of individuals at the 6-month, 12-month, and 24-month examinations, respectively, indicating a 10.3% 2-year diabetes incidence. Mean (95% CI) increases from baseline to 2-year follow-up were 0.30 (0.29 to 0.32) percentage points (3.3 (3.2 to 3.5) mmol/mol) for Hemoglobin A 1c, 0.13 (0.10 to 0.16) mmol/L for fasting serum-glucose, 0.46 (0.36 to 0.56) mmol/L for 2-hour OGTT s-glucose, 0.30 (0.19 to 0.40) kg/m(2) forbody mass index (BMI) (all p<0.001) and -0.5 (-0.9 to -0.2) cm for waist circumference (p= 0.004), with broadly similar estimates by baseline age, sex, education, depressive symptoms, BMI, physical activity, and family history of diabetes. Only 206 (8.7%) participants had evidence of > 5% weight loss during follow-up; their fasting and 2-hour s-glucose did not increase, and HbA 1c increased less than in other participants. Conclusion Basic lifestyle advice given to high-risk individuals during three group sessions with 6-month intervals was not effective in reducing 2-year diabetes risk.
  • Bjorkman, Mikko P.; Pitkala, Kaisu H.; Jyvakorpi, Satu; Strandberg, Timo E.; Tilvis, Reijo S. (2019)
    Objectives: To assess the prognostic significance of various characteristics and measurements of sarcopenia and physical functioning on all-cause mortality among home-dwelling older people with or at-risk of sarcopenia. Design: Cross-sectional and longitudinal analyses. Setting: Porvoo sarcopenia trial in open care. Participants: Community-dwelling people aged 75 and older (N = 428, of which 182 were re-examined at one year) with four years of follow-up. Measurements: Body mass index (BMI), physical functioning (physical component of the RAND-36) and physical performance tests (Short Physical Performance Battery (SPPB)), hand grip strength, walking speed, Charlson Comorbity Index, bioimpedance-based surrogates for muscle mass: Single Frequency Skeletal Muscle Index (SF-SMI), and Calf Intracellular Resistance Skeletal Muscle Index (CRi-SMI). Date of death was retrieved from central registers. Survival analyses were performed using Life-Table analyses and Cox models. Results: Most test variables (except BMI) were associated with four-year mortality in a dose-dependent fashion. After controlling for age, gender and co-morbidity, physical performance and functioning (both SPPB and RAND36), muscle strength (hand grip strength) and CRi-SMI appeared to be independent mortality risk indicators (p <0.001) whereas SF-SMI was not. When CRi-SMI values were grouped by gender-specific cut-off points, the probability of surviving for four years decreased by 66% among the older people with low CRi-SMI (HR = 0.34, 95%CI 0.15-0.78, p = 0.011). When low CRi-SMI was further controlled for SPPB, the prognostic significance remained significant (HR = 0.55, 95%CI 0.33-0.92, p = 0.021). After controlling for age, gender, comorbidity, and CRi-SMI, the physical component of the RAND-36 (p = 0.007), SPPB (p <0,001) and hand grip strength (p = 0.009) remained significant mortality predictors. Twelve-month changes were similarly associated with allcause mortality during the follow-up period. Conclusion: CRi-SMI, muscle strength, physical performance and physical functioning are each strong independent predictors of all-cause mortality among home-dwelling older people. Compared to these indicators, BMI seemed to be clearly inferior. Of two bioimpedance-based muscle indices, CRi SMI was better predictor of mortality than SF-SMI. In this regard, muscle mass, muscle strength and physical performance are all suitable targets for the prevention of sarcopenia-related over-mortality.
  • Biesiekierski, Jessica R.; Jalanka, Jonna; Staudacher, Heidi M. (2019)
    Dietary intervention is a challenge in clinical practice because of inter-individual variability in clinical response. Gut microbiota is mechanistically relevant for a number of disease states and consequently has been incorporated as a key variable in personalised nutrition models within the research context. This paper aims to review the evidence related to the predictive capacity of baseline microbiota for clinical response to dietary intervention in two specific health conditions, namely, obesity and irritable bowel syndrome (IBS). Clinical trials and larger predictive modelling studies were identified and critically evaluated. The findings reveal inconsistent evidence to support baseline microbiota as an accurate predictor of weight loss or glycaemic response in obesity, or as a predictor of symptom improvement in irritable bowel syndrome, in dietary intervention trials. Despite advancement in quantification methodologies, research in this area remains challenging and larger scale studies are needed until personalised nutrition is realistically achievable and can be translated to clinical practice.
  • Ervasti, Jenni; Airaksinen, Jaakko; Pentti, Jaana; Vahtera, Jussi; Suominen, Sakari; Virtanen, Marianna; Kivimäki, Mika (2019)
    Objectives We examined the extent to which an increase in physical activity would reduce the excess risk of work disability among overweight and obese people (body mass index >= 25kg/m(2)). Methods We used counterfactual modelling approaches to analyze longitudinal data from two Finnish prospective cohort studies (total N=38 744). Weight, height and physical activity were obtained from surveys and assessed twice and linked to electronic records of two indicators of long-term work disability (>= 90-day sickness absence and disability pension) for a 7-year follow-up after the latter survey. The models were adjusted for age, sex, socioeconomic status, smoking, and alcohol consumption. Results The confounder-adjusted hazard ratio (HR) of long-term sickness absence for overweight compared to normal-weight participants was 1.43 [95% confidence interval (CI) 1.35-1.53]. An increase in physical activity among overweight compared to normal-weight individuals was estimated to reduce this HR to 1.40 (95% CI 1.31-1.48). In pseudo-trial analysis including only the persistently overweight, initially physically inactive participants, the HR for long-term sickness absence was 0.82 (95% CI 0.70-0.94) for individuals with increased physical activity compared to those who remained physically inactive. The results for disability pension as an outcome were similar. Conclusions These findings suggest that the excess risk of work disability among overweight individuals would drop by 3-4% if they increased their average physical activity to the average level of normal-weight people. However, overweight individuals who are physically inactive would reduce their risk of work disability by about 20% by becoming physically active.
  • Luukkonen, Panu K.; Dufour, Sylvie; Lyu, Kun; Zhang, Xian-Man; Hakkarainen, Antti; Lehtimäki, Tiina E.; Cline, Gary W.; Petersen, Kitt Falk; Shulman, Gerald I.; Yki-Järvinen, Hannele (2020)
    Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope infusions of: [D-7]glucose, [C-13(4)]beta-hydroxybutyrate and [3-C-13]lactate before and after a 6-d KD. IHTG was determined by proton magnetic resonance spectroscopy (H-1-MRS). The KD diet decreased IHTG by 31% in the face of a 3% decrease in body weight and decreased hepatic insulin resistance (-58%) despite an increase in NEFA concentrations (+35%). These changes were attributed to increased net hydrolysis of IHTG and partitioning of the resulting fatty acids toward keto-genesis (+232%) due to reductions in serum insulin concentrations (-53%) and hepatic citrate synthase flux (-38%), respectively. The former was attributed to decreased hepatic insulin resistance and the latter to increased hepatic mitochondrial redox state (+167%) and decreased plasma leptin (-45%) and triiodothyronine (-21%) concentrations. These data demonstrate heretofore unde-scribed adaptations underlying the reversal of NAFLD by KD: That is, markedly altered hepatic mitochondrial fluxes and redox state to promote ketogenesis rather than synthesis of IHTG.
  • Reinders, Ilse; Wijnhoven, Hanneke A. H.; Jyväkorpi, Satu K.; Suominen, Merja H.; Niskanen, Riikka; Bosmans, Judith E.; Brouwer, Ingeborg A.; Fluitman, Kristien S.; Klein, Michel C. A.; Kuijper, Lothar D.; van der Lubbe, Laura M.; Olthof, Margreet R.; Pitkälä, Kaisu H.; Vijlbrief, Rachel; Visser, Marjolein (2020)
    Introduction Short-term metabolic and observational studies suggest that protein intake above the recommended dietary allowance of 0.83 g/kg body weight (BW)/day may support preservation of lean body mass and physical function in old age, but evidence from randomised controlled trials is inconclusive. Methods and analysis The PRevention Of Malnutrition In Senior Subjects in the EU (PROMISS) trial examines the effect of personalised dietary advice aiming at increasing protein intake with or without advice regarding timing of protein intake to close proximity of usual physical activity, on change in physical functioning after 6 months among community-dwelling older adults (>= 65 years) with a habitual protein intake of Discussion The PROMISS trial will provide evidence whether increasing protein intake, and additionally optimising the timing of protein intake, has a positive effect on the course of physical functioning after 6 months among community-dwelling older adults with a habitual protein intake of Ethics and dissemination The study has been approved by the Ethics Committee of the Helsinki University Central Hospital, Finland (ID of the approval: HUS/1530/2018) and The Medical Ethical Committee of the Amsterdam UMC, location VUmc, Amsterdam, the Netherlands (ID of the approval: 2018.399). All participants provided written informed consent prior to being enrolled onto the study. Results will be submitted for publication in peer-reviewed journals and will be made available to stakeholders (ie, older adults, healthcare professionals and industry).
  • Nurmi, Johanna; Knittle, Keegan; Ginchev, Todor; Khattak, Fida; Helf, Christopher; Zwickl, Patrick; Castellano-Tejedor, Carmina; Lusilla-Palacios, Pilar; Costa-Requena, Jose; Ravaja, Niklas; Haukkala, Ari (2020)
    Background: Most adults do not engage in sufficient physical activity to maintain good health. Smartphone apps are increasingly used to support physical activity but typically focus on tracking behaviors with no support for the complex process of behavior change. Tracking features do not engage all users, and apps could better reach their targets by engaging users in reflecting their reasons, capabilities, and opportunities to change. Motivational interviewing supports this active engagement in self-reflection and self-regulation by fostering psychological needs proposed by the self-determination theory (ie, autonomy, competence, and relatedness). However, it is unknown whether digitalized motivational interviewing in a smartphone app engages users in this process. Objective: This study aimed to describe the theory- and evidence-based development of the Precious app and to examine how digitalized motivational interviewing using a smartphone app engages users in the behavior change process. Specifically, we aimed to determine if use of the Precious app elicits change talk in participants and how they perceive autonomy support in the app. Methods: A multidisciplinary team built the Precious app to support engagement in the behavior change process. The Precious app targets reflective processes with motivational interviewing and spontaneous processes with gamified tools, and builds on the principles of self-determination theory and control theory by using 7 relational techniques and 12 behavior change techniques. The feasibility of the app was tested among 12 adults, who were asked to interact with the prototype and think aloud. Semistructured interviews allowed participants to extend their statements. Participants’ interactions with the app were video recorded, transcribed, and analyzed with deductive thematic analysis to identify the theoretical themes related to autonomy support and change talk. Results: Participants valued the autonomy supportive features in the Precious app (eg, freedom to pursue personally relevant goals and receive tailored feedback). We identified the following five themes based on the theory-based theme autonomy support: valuing the chance to choose, concern about lack of autonomy, expecting controlling features, autonomous goals, and autonomy supportive feedback. The motivational interviewing features actively engaged participants in reflecting their outcome goals and reasons for activity, producing several types of change talk and very little sustain talk. The types of change talk identified were desire, need, reasons, ability, commitment, and taking steps toward change. Conclusions: The Precious app takes a unique approach to engage users in the behavior change process by targeting both reflective and spontaneous processes. It allows motivational interviewing in a mobile form, supports psychological needs with relational techniques, and targets intrinsic motivation with gamified elements. The motivational interviewing approach shows promise, but the impact of its interactive features and tailored feedback needs to be studied over time. The Precious app is undergoing testing in a series of n-of-1 randomized controlled trials. KEYWORDS health app; mHealth; human-computer interaction; prevention; service design; usability design; intrinsic motivation; reflective processes; spontaneous processes; engagement; self-determination theory; autonomous motivation; gamification; physical activity
  • Honkala, Sanna Maria; Motiani, Piryanka; Kivelä, Riikka; Hemanthakumar, Karthik Amudhala; Tolvanen, Erik; Motiani, Kumail Kumar; Eskelinen, Jari-Joonas; Virtanen, Kirsi A.; Kemppainen, Jukka; Heiskanen, Marja Anneli; Loyttyniemi, Eliisa; Nuutila, Pirjo; Kalliokoski, Kari K.; Hannukainen, Jarna Christina (2020)
    Introduction We investigated the effects of a supervised progressive sprint interval training (SIT) and moderate-intensity continuous training (MICT) on adipocyte morphology and adipose tissue metabolism and function; we also tested whether the responses were similar regardless of baseline glucose tolerance and sex. Research design and methods 26 insulin-resistant (IR) and 28 healthy participants were randomized into 2-week-long SIT (4-6x30 s at maximum effort) and MICT (40-60 min at 60% of maximal aerobic capacity (VO2peak)). Insulin-stimulated glucose uptake and fasting-free fatty acid uptake in visceral adipose tissue (VAT), abdominal and femoral subcutaneous adipose tissues (SATs) were quantified with positron emission tomography. Abdominal SAT biopsies were collected to determine adipocyte morphology, gene expression markers of lipolysis, glucose and lipid metabolism and inflammation. Results Training increased glucose uptake in VAT (p
  • Nettleton, Jennifer A.; Follis, Jack L.; Ngwa, Julius S.; Smith, Caren E.; Ahmad, Shafqat; Tanaka, Toshiko; Wojczynski, Mary K.; Voortman, Trudy; Lemaitre, Rozenn N.; Kristiansson, Kati; Nuotio, Marja-Liisa; Houston, Denise K.; Perala, Mia-Maria; Qi, Qibin; Sonestedt, Emily; Manichaikul, Ani; Kanoni, Stavroula; Ganna, Andrea; Mikkila, Vera; North, Kari E.; Siscovick, David S.; Harald, Kennet; Mckeown, Nicola M.; Johansson, Ingegerd; Rissanen, Harri; Liu, Yongmei; Lahti, Jari; Hu, Frank B.; Bandinelli, Stefania; Rukh, Gull; Rich, Stephen; Booij, Lisanne; Dmitriou, Maria; Ax, Erika; Raitakari, Olli; Mukamal, Kenneth; Mannisto, Satu; Hallmans, Goran; Jula, Antti; Ericson, Ulrika; Jacobs, David R.; Van Rooij, Frank J. A.; Deloukas, Panos; Sjogren, Per; Kahonen, Mika; Djousse, Luc; Perola, Markus; Barroso, Ines; Hofman, Albert; Stirrups, Kathleen; Viikari, Jorma; Uitterlinden, Andre G.; Kalafati, Ioanna P.; Franco, Oscar H.; Mozaffarian, Dariush; Salomaa, Veikko; Borecki, Ingrid B.; Knekt, Paul; Kritchevsky, Stephen B.; Eriksson, Johan G.; Dedoussis, George V.; Qi, Lu; Ferrucci, Luigi; Orho-Melander, Marju; Zillikens, M. Carola; Ingelsson, Erik; Lehtimaki, Terho; Renstrom, Frida; Cupples, L. Adrienne; Loos, Ruth J. F.; Franks, Paul W. (2015)
    Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
  • Liu, Ching-Ti; Merino, Jordi; Rybin, Denis; DiCorpo, Daniel; Benke, Kelly S.; Bragg-Gresham, Jennifer L.; Canouil, Mickaël; Corre, Tanguy; Grallert, Harald; Isaacs, Aaron; Kutalik, Zoltan; Lahti, Jari; Marullo, Letizia; Marzi, Carola; Rasmussen-Torvik, Laura J.; Rocheleau, Ghislain; Rueedi, Rico; Scapoli, Chiara; Verweij, Niek; Vogelzangs, Nicole; Willems, Sara M.; Yengo, Loïc; Bakker, Stephan J. L.; Beilby, John; Hui, Jennie; Kajantie, Eero; Müller-Nurasyid, Martina; Rathmann, Wolfgang; Balkau, Beverley; Bergmann, Sven; Eriksson, Johan G.; Florez, Jose C.; Froguel, Philippe; Harris, Tamara; Hung, Joseph; James, Alan L.; Kavousi, Maryam; Miljkovic, Iva; Musk, Arthur W.; Palmer, Lyle J.; Peters, Annette; Roussel, Ronan; van der harst, Pim; van Duijn, Cornelia M.; Vollenweider, Peter; Barroso, Inês; Prokopenko, Inga; Dupuis, Josée; Meigs, James B.; Bouatia-Naji, Nabila (2019)
    Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 x 10(-8)) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.
  • Rounge, Trine B.; Page, Christian M.; Lepistö, Maija; Ellonen, Pekka; Andreassen, Bettina K.; Weiderpass, Elisabete (2016)
    Aim: We performed an epigenome-wide association study within the Finnish Health in Teens cohort to identify differential DNA methylation and its association with BMI in adolescents. Materials & methods: Differential DNA methylation analyses of 3.1 million CpG sites were performed in saliva samples from 50 lean and 50 heavy adolescent girls by genome-wide targeted bisulfite-sequencing. Results: We identified 100 CpG sites with p-values <0.000524, seven regions by 'bumphunting' and five CpG islands that differed significantly between the two groups. The ten CpG sites and regions most strongly associated with BMI substantially overlapped with obesity-and insulin-related genes, including MC2R, IGFBPL1, IP6K1 and IGF2BP1. Conclusion: Our findings suggest an association between the saliva methylome and BMI in adolescence.
  • Kilpelainen, Tuomas O.; Carli, Jayne F. Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F.; Hedman, Asa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H.; Schick, Ursula; Grarup, Niels; Kutalik, Zoltan; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikainen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renstrom, Frida; Willems, Sara M.; Mahajan, Anubha; Rose, Lynda M.; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E.; Perusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S.; Sung, Yun Ju; Ramos, Yolande F.; Amin, Najaf; Amuzu, Antoinette; Barroso, Ines; Bellis, Claire; Blangero, John; Buckley, Brendan M.; Boehringer, Stefan; Chen, Yii-Der I.; de Craen, Anton J. N.; Crosslin, David R.; Dale, Caroline E.; Dastani, Zari; Day, Felix R.; Deelen, Joris; Delgado, Graciela E.; Demirkan, Ayse; Finucane, Francis M.; Ford, Ian; Garcia, Melissa E.; Gieger, Christian; Gustafsson, Stefan; Hallmans, Goran; Hankinson, Susan E.; Havulinna, Aki S.; Herder, Christian; Hernandez, Dena; Hicks, Andrew A.; Hunter, David J.; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S.; Jorgensen, Marit E.; Jorgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A.; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P.; Myers, Richard H.; Mannisto, Satu; Nalls, Mike A.; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rathmann, Wolfgang; Rice, Treva K.; Richards, J. Brent; Ridker, Paul M.; Sattar, Naveed; Savage, David B.; Soderberg, Stefan; Timpson, Nicholas J.; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widen, Elisabeth; Wood, Andrew R.; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sorensen, Thorkild I. A.; Sarzynski, Mark A.; Rao, D. C.; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G.; Heliovaara, Markku; Knekt, Paul B.; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K.; Viikari, Jorma S.; Kahonen, Mika; Lehtimaki, Terho; Raitakari, Olli T.; Mellstrom, Dan; Lorentzon, Mattias; Casas, Juan P.; Bandinelli, Stefanie; Maerz, Winfried; Isaacs, Aaron; van Dijk, Ko W.; van Duijn, Cornelia M.; Harris, Tamara B.; Bouchard, Claude; Allison, Matthew A.; Chasman, Daniel I.; Ohlsson, Claes; Lind, Lars; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; Ferrucci, Luigi; Frayling, Timothy M.; Pramstaller, Peter P.; Borecki, Ingrid B.; Waterworth, Dawn M.; Bergmann, Sven; Waeber, Gerard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B.; Slagboom, P. Eline; Grallert, Harald; Spector, Tim D.; Jukema, J. W.; Klein, Robert J.; Schadt, Erik E.; Franks, Paul W.; Lindgren, Cecilia M.; Leibel, Rudolph L.; Loos, Ruth J. F. (2016)
    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P <10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P <5 x 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
  • Korpela, Katri; Flint, Harry J.; Johnstone, Alexandra M.; Lappi, Jenni; Poutanen, Kaisa; Dewulf, Evelyne; Delzenne, Nathalie; de Vos, Willem M.; Salonen, Anne (2014)
  • Møller, Grith; Rikardt Andersen, Jens; Ritz, Christian; P. Silvestre, Marta; Navas-Carretero, Santiago; Jalo, Elli; Christensen, Pia; Simpson, Elizabeth; Taylor, Moira; Martinez, J. Alfredo; Macdonald, Ian; Swindell, Nils; Mackintosh, Kelly A.; Stratton, Gareth; Fogelholm, Mikael; Larsen, Thomas M.; Poppitt, Sally D.; Dragsted, Lars O.; Raben, Anne (2018)
    Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic men and women, aged 55 years and older. Analyses were based on baseline and one-year data in a sub-group of 310 participants included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World). Protein intake was estimated from four-day dietary records and 24-hour urinary urea excretion. We used linear regression to assess the association between protein intake after one year of intervention and kidney function markers: creatinine clearance, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (ACR), urinary urea/creatinine ratio (UCR), serum creatinine, and serum urea before and after adjustments for potential confounders. A higher protein intake was associated with a significant increase in UCR (p = 0.03) and serum urea (p = 0.05) after one year. There were no associations between increased protein intake and creatinine clearance, eGFR, ACR, or serum creatinine. We found no indication of impaired kidney function after one year with a higher protein intake in pre-diabetic older adults.
  • Luukkonen, Panu K.; Nick, Auli; Hölttä-Vuori, Maarit; Thiele, Christoph; Isokuortti, Elina; Lallukka-Brück, Susanna; Zhou, You; Hakkarainen, Antti; Lundbom, Nina; Peltonen, Markku; Orho-Melander, Marju; Oresic, Matej; Hyötyläinen, Tuulia; Hodson, Leanne; Ikonen, Elina; Yki-Järvinen, Hannele (2019)
    The common patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant I148M predisposes to nonalcoholic liver disease but not its metabolic sequelae. We compared the handling of labeled polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFA) in vivo in humans and in cells harboring different PNPLA3 genotypes. In 148M homozygous individuals, triglycerides (TGs) in very low-density lipoproteins (VIOL) were depleted of PUFAs both under fasting and postprandial conditions compared with 148I homozygotes, and the PUFA/SFA ratio in VLDL-TGs was lower relative to the chylomicron precursor pool. In human PNPLA3-148M and PNPLA3-KO cells, PUFA but not SFA incorporation into TGs was increased at the expense of phosphatidylcholines, and under lipolytic conditions, PUFA-containing diacylglycerols (DAGs) accumulated compared with PNPLA3-148I cells. Polyunsaturated TGs were increased, while phosphatidylcholines (PCs) were decreased in the human liver in 148M homozygous individuals as compared with 148I homozygotes. We conclude that human PNPLA3-I148M is a loss-of-function allele that remodels liver TGs in a polyunsaturated direction by impairing hydrolysis/transacylation of PUFAs from DAGs to feed phosphatidylcholine synthesis.
  • Rintamäki, Reeta; Rautio, Nina; Peltonen, Markku; Jokelainen, Jari; Keinänen-Kiukaanniemi, Sirkka; Oksa, Heikki; Saaristo, Timo; Puolijoki, Hannu; Saltevo, Juha; Tuomilehto, Jaakko; Uusitupa, Matti; Moilanen, Leena (2021)
    Aims: The Finnish National Diabetes Prevention Program (FIN-D2D) was the first large-scale diabetes prevention program in a primary health care setting in the world. The risk reduction of type 2 diabetes was 69% after one-year intervention in high-risk individuals who were able to lose 5% of their weight. We investigated long-term effects of one-year weight change on the incidence of type 2 diabetes, cardiovascular events, and all-cause mortality. Methods: A total of 10,149 high-risk individuals for type 2 diabetes were identified in primary health care centers and they were offered lifestyle intervention to prevent diabetes. Of these individuals who participated in the baseline screening, 8353 had an oral glucose tolerance test (OGTT). Complete followup data during one-year intervention were available for 2730 individuals and those were included in the follow-up analysis. The long-term outcome events were collected from national health registers after the median follow-up of 7.4 years. Results: Among individuals who lost weight 2.5 & minus;4.9% and 5% or more during the first year, the hazard ratio for the incidence of drug-treated diabetes was 0.63 (95% CI 0.49 & minus;0.81, p = 0.0001), and 0.71 (95% CI 0.56 & minus;0.90, p = 0.004), respectively, compared with those with stable weight. There were no significant differences in cardiovascular events or all-cause mortality among study participants according to oneyear weight changes. Conclusions: High-risk individuals for type 2 diabetes who achieved a moderate weight loss by one-year lifestyle counseling in primary health care had a long-term reduction in the incidence of drug-treated type 2 diabetes. The observed moderate weight loss was not associated with a reduction in cardiovascular events. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).
  • Ratia, Nadja; Pietiläinen, Kirsi H.; Auranen, Mari; Saksa, Lauri; Luukkonen, Ritva; Suomalainen, Anu; Piirilä, Päivi (2021)
    Background: Low-carbohydrate diets, including the modified Atkins diet (mAD), are commonly used to promote weight loss, improve exercise performance, and treat refractory epilepsy and inherited metabolism disorders. However, the effects of the high-fat-low-carbohydrate diet on the physiology of healthy subjects still need further study. We evaluated the physiological influence of mAD on cardiopulmonary exercise results in healthy adult subjects. Materials and methods: Ten healthy volunteers followed mAD for four weeks with laboratory follow-up. Cardiopulmonary exercise tests were performed before, and at the end of mAD, and venous lactate, ammonia, and blood gases were collected before, during, and after exercise testing. Results and conclusions: Four-week mAD decreased the subjects' mechanical efficiency in the cardiopulmonary exercise test and caused increased ventilation and decreased fraction of expired CO2 in maximal exercise. This evidence suggests that mAD can cause hyperventilation tendency at least in the short term, a possible adverse effect of the diet.
  • Alligier, Maud; Barres, Romain; Blaak, Ellen E.; Boirie, Yves; Bouwman, Jildau; Brunault, Paul; Campbell, Kristina; Clement, Karine; Farooqi, I. Sadaf; Farpour-Lambert, Nathalie J.; Fruhbeck, Gema; Goossens, Gijs H.; Hager, Jorg; Halford, Jason C. G.; Hauner, Hans; Jacobi, David; Julia, Chantal; Langin, Dominique; Natali, Andrea; Neovius, Martin; Oppert, Jean Michel; Pagotto, Uberto; Palmeira, Antonio L.; Roche, Helen; Ryden, Mikael; Scheen, Andre J.; Simon, Chantal; Sorensen, Thorkild I. A.; Tappy, Luc; Yki-Järvinen, Hannele; Ziegler, Olivier; Laville, Martine (2020)
    Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes.