China
Africa
Explore chapters and articles related to this topic
The metabolic basis of obesity
Published in Anna Bellisari, The Anthropology Of Obesity in the United States, 2016
In the decades since the concept of the thrifty genotype was proposed, new technologies such as human genome mapping and genome-wide association studies (GWAS) have identified 75 obesity-susceptibility genetic variants (Loos and Yeo 2014). Only about 5 percent of all cases of obesity are single-gene disorders, influenced by mutations in a few major-effect genes such as LEP and LEPR. Many more moderate-effect gene variants (for example, FAIM2, BDNF, ETV5, FTO, GNPDA2, KCTD15, MC4R, MTCH2, NEGR1, SEC16B, SH2B1, TMEM18) are associated with most cases of obesity (Li et al. 2010). Their effects are additive – individuals who carry more of the known risk alleles have higher BMI levels than those who have inherited fewer of them. Recently new genetic techniques have been used to identify more than 100 obesity-related genetic loci linked to hypothalamic regulation of adiposity, appetite control, development and differentiation of adipocytes, and other biological processes involved in metabolism and fat distribution (Locke et al. 2015; Shungin et al. 2015).
Association of the NEGR1 rs2815752 with obesity and related traits in Pakistani females
Published in Upsala Journal of Medical Sciences, 2020
Neuronal growth regulator 1 (NEGR1) has recently been identified as a new locus responsible for human body weight control in three independent GWAS (8–10). The NEGR1 gene is positioned on chromosome 1p31.1 and is mainly expressed in the hypothalamus (a crucial center for energy balance and regulation of food intake). However, it is also expressed in subcutaneous adipose tissue (SAT), heart, and skeletal muscles (11). Differential co-expression analysis of obesity-associated networks in human subcutaneous adipose tissue revealed differential expression of the NEGR1 gene between normal-weight and obese siblings with identification of NEGR1 as a central hub in an obesity-related transcript network (12). However, in vivo studies have shown varying results for correlation between the expression level of NEGR1 and manifestation of obesity, perhaps owing to highly complex regulatory processes of energy homeostasis. The functional inactivation of NEGR1 in mice led to a small but steady decrease in body mass. In addition, mice carrying a loss-of-function mutation (NEGR1-I87N) showed decreased food intake but normal energy expenditure, thereby supporting the positive correlation between NEGR1 expression and obesity (13). However, another in vivo study involving the use of an adeno-associated virus revealed that the decreased expression of NEGR1 in periventricular hypothalamic areas of rats resulted in escalated bodyweight presumably via increased food intake, but NEGR1 overexpression did not affect body weight or food intake (14).