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      Impact of Genetic Variants on the Individual Potential for Body Fat Loss

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          Abstract

          The past decade has witnessed the discovery of obesity-related genetic variants and their functions through genome-wide association studies. Combinations of risk alleles can influence obesity phenotypes with different degrees of effectiveness across various individuals by interacting with environmental factors. We examined the interaction between genetic variation and changes in dietary habits or exercise that influences body fat loss from a large Korean cohort ( n = 8840). Out of 673 obesity-related SNPs, a total of 100 SNPs (37 for carbohydrate intake; 19 for fat intake; 44 for total calories intake; 25 for exercise onset) identified to have gene-environment interaction effect in generalized linear model were used to calculate genetic risk scores (GRS). Based on the GRS distribution, we divided the population into four levels, namely, “very insensitive”, “insensitive”, “sensitive”, and “very sensitive” for each of the four categories, “carbohydrate intake”, “fat intake”, “total calories intake”, and “exercise”. Overall, the mean body fat loss became larger when the sensitivity level was increased. In conclusion, genetic variants influence the effectiveness of dietary regimes for body fat loss. Based on our findings, we suggest a platform for personalized body fat management by providing the most suitable and effective nutrition or activity plan specific to an individual.

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          Most cited references32

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          An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma).

          Thiazolidinedione derivatives are antidiabetic agents that increase the insulin sensitivity of target tissues in animal models of non-insulin-dependent diabetes mellitus. In vitro, thiazolidinediones promote adipocyte differentiation of preadipocyte and mesenchymal stem cell lines; however, the molecular basis for this adipogenic effect has remained unclear. Here, we report that thiazolidinediones are potent and selective activators of peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the nuclear receptor superfamily recently shown to function in adipogenesis. The most potent of these agents, BRL49653, binds to PPAR gamma with a Kd of approximately 40 nM. Treatment of pluripotent C3H10T1/2 stem cells with BRL49653 results in efficient differentiation to adipocytes. These data are the first demonstration of a high affinity PPAR ligand and provide strong evidence that PPAR gamma is a molecular target for the adipogenic effects of thiazolidinediones. Furthermore, these data raise the intriguing possibility that PPAR gamma is a target for the therapeutic actions of this class of compounds.
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            15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma.

            Regulation of adipose cell mass is a critical homeostatic process in higher vertebrates. The conversion of fibroblasts into cells of the adipose lineage is induced by expression of the orphan nuclear receptor PPAR gamma. This suggests that an endogenous PPAR gamma ligand may be an important regulator of adipogenesis. By assaying arachidonate metabolites for their capacity to activate PPAR response elements, we have identified 15-deoxy-delta 12, 14-prostaglandin J2 as both a PPAR gamma ligand and an inducer of adipogenesis. Similarly, the thiazolidinedione class of antidiabetic drugs also bind to PPAR gamma and act as potent regulators of adipocyte development. Thus, adipogenic prostanoids and antidiabetic thiazolidinediones initiate key transcriptional events through a common nuclear receptor signaling pathway. These findings suggest a pivotal role for PPAR gamma and its endogenous ligand in adipocyte development and glucose homeostasis and as a target for intervention in metabolic disorders.
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              Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans.

              A BMI in the normal range associates with a decreased risk of cardiometabolic disease and all-cause mortality. However, not all subjects in this BMI range have this low risk. Compared to people who are of normal weight and metabolically healthy, subjects who are of normal weight but metabolically unhealthy (∼20% of the normal weight adult population) have a greater than 3-fold higher risk of all-cause mortality and/or cardiovascular events. Here we address to what extent major risk phenotypes determine metabolic health in lean compared to overweight and obese people and provide support for the existence of a lipodystrophy-like phenotype in the general population. Furthermore, we highlight the molecular mechanisms that induce this phenotype. Finally, we propose strategies as to how this knowledge could be implemented in the prevention and treatment of cardiometabolic diseases in different stages of adiposity in routine clinical practice.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                26 February 2018
                March 2018
                : 10
                : 3
                : 266
                Affiliations
                [1 ]Samsung Genome Institute, Samsung Medical Center, Gangnam-gu, Seoul 06351, Korea; scha@ 123456ncsu.edu (S.C.); kangx342@ 123456gmail.com (J.H.K.); noonolee@ 123456gmail.com (J.-H.L.); wonniey@ 123456gmail.com (H.K.)
                [2 ]Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Gyeonggi-do, Korea
                [3 ]Software R&D Center, Samsung Electronics, Hwaseong 18448, Gyeonggi-do, Korea; jk.neo.kim@ 123456samsung.com
                [4 ]Department of Food and Nutrition, Dongduk Women’s University, Seoul 02748, Korea; yjyang@ 123456dongduk.ac.kr
                Author notes
                [* ]Correspondence: woongyang.park@ 123456samsung.com (W.-Y.P.); jinho.jk.kim@ 123456samsung.com or jinho80@ 123456gmail.com (J.K.); Tel.: +82-2-3410-6128 (W.-Y.P.); Tel.: +82-2-2148-9847 (J.K.)
                Author information
                https://orcid.org/0000-0003-2269-4536
                https://orcid.org/0000-0001-9395-0854
                https://orcid.org/0000-0001-9524-9981
                Article
                nutrients-10-00266
                10.3390/nu10030266
                5872684
                29495392
                429a059f-38e1-46cc-a670-ff99331c1910
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 December 2017
                : 23 February 2018
                Categories
                Article

                Nutrition & Dietetics
                gwas,bmi,body fat,obesity,diet,health,exercise,genetic risk score
                Nutrition & Dietetics
                gwas, bmi, body fat, obesity, diet, health, exercise, genetic risk score

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