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Applications of Pluripotent Stem Cells in the Therapy and Modeling of Diabetes and Metabolic Diseases
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Suranjit Mukherjee, Shuibing Chen
In the pathogenesis of obesity-linked T2DM, the adipose tissue becomes increasingly insulin resistant, resulting in less glucose uptake and increased hydrolysis of stored lipids. These free fatty acids then enter circulation and deposit in the muscle and the liver, leading to steatosis and tissue dysfunction. Attempts to elucidate the mechanism underlying adipose tissue expansion and insulin resistance have revealed that in mouse models of obesity, the expansion of adipocytes in response to increasing triacylglyceride content leads to a lipotoxicity that recruits macrophages and other inflammatory cell types, setting off a series of cytokine events that are linked to insulin resistance (2). GWASs have also helped shed light on some of the genetic components behind predispositions to obesity, with the identification of SNPs in PPARγ and polymorphisms in the FTO gene, being highly correlated to obesity and T2DM (28,29).
The sex-specific influence of FTO genotype on exercise intervention for weight loss in adult with obesity
Published in European Journal of Sport Science, 2022
Weimin Wang, Ke Yang, Shujie Wang, Jiani Zhang, Yanyun Shi, Huawei Zhang, Danping Jin, Ruoxi Gu, Qiang Zeng, Qian Hua
To our best knowledge, this is the first study performed on the Han Chinese population to investigate the impact of FTO on weight change after exercise intervention. Since the FTO gene was first identified in 2007, the studies confirming the FTO as a risk factor for obesity have been replicated in most populations, especially Caucasians. Compared with those not inheriting a risk allele in English descent, people with allele (AA) weigh on average about 3 kg greater and have a 1.7-fold increased possibility to be obese (Frayling et al., 2007). Many other subsequent studies have also validated the association between FTO and obesity in European countries (Dina et al., 2007; Hinney et al., 2007; Scuteri et al., 2007). However, the controversial results also exist, suggesting that ethnicity and gender may underlie the association (Jacobsson et al., 2008; Zdrojowy-Wełna et al., 2020). As for the Han Chinese population, the earliest study concluded that there was no such association (Li et al., 2008). In contrast, a later study on Chinese living in Singapore reached the opposite result (Tan et al., 2008). Moreover, a recent study indicated that FTO also influenced the extreme type of obesity (morbid obesity) in the Chinese population (Chiang et al., 2019).
The genetic predisposition to obesity has no influence on waist circumference when screen time and sleep duration are adequate in children and adolescents
Published in European Journal of Sport Science, 2022
Caroline Brand, Ana Paula Sehn, Pâmela Ferreira Todendi, Andreia Rosane de Moura Valim, Vanessa Suñé Mattevi, Antônio García-Hermoso, Anelise Reis Gaya, Cézane Priscila Reuter
Obesity in all ages is a critical concern worldwide due to the detrimental effects on health, including the development of type 2 diabetes, hypertension, and metabolic syndrome (Halfon, Verhoef, & Kuo, 2012; Xi, 2019). It is widely accepted that it is determined by the interplay between environmental factors and genetic susceptibility (Albuquerque, Nóbrega, & Manco, 2017; Sheikh et al., 2017). Among obesity-associated genetic factors, the rs9939609 single nucleotide polymorphism (SNP), which was identified in the first intron of fat mass and obesity associated gene (FTO), has been widely studied and established as exerting an influence in obesity among adults and youth (Jiang et al., 2019; Mehrdad, Fardaei, Fararouei, & Eftekhari, 2020; Mozafarizadeh et al., 2019; Ning et al., 2019), that is schoolchildren with the risk genotype (AA allele) showed 3.21% higher chance of presenting obesity (Reuter et al., 2016). The FTO gene role in obesity and associated phenotypes was first described in 2007, in a genome-wide association study searching for genes associated with type 2 diabetes (Loos & Yeo, 2014). Since this gene is highly expressed in the hypothalamus, it is believed to play a fundamental role in the control of energy homeostasis, although the exact mechanism is still a matter of controversy (Loos & Yeo, 2014).