Fat Mass and Obesity Associated (FTO) Gene and Hepatic Glucose and Lipid Metabolism

Abstract

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed, but appears to have tissue-specific roles. Earlier studies have focused on the role of hypothlamic FTO in the regulation of metabolism. However, it appears that FTO plays a role in the regulation of metabolism in a tissue-specific manner. Recent studies suggest that expression of hepatic FTO is regulated by metabolic signals such as nutrients and hormones and altered FTO levels in liver affects glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

Association of FTO rs9939609 polymorphism with serum leptin, insulin, adiponectin, and lipid profile in overweight adults

“…Finally, we can claim that the effect size of A-allele on HDL-c and leptin is approximately close to the effect size in the European population; thus, we can conclude that the associations and effect size of this variant in this population is similar to those in Europeans, since our population is Caucasians as Europeans [16,27]. Evidences showed that this gene can regulate lipid profile through hepatic signalling pathways; however, the exact mechanism is not yet understood [34,35] Since HDL-c level is strongly associated with noncommunicating diseases, based on these findings, carriers of A-allele might be more susceptible to metabolic disturbances and subsequently affected by non-communicating diseases such as metabolic syndrome, cardiovascular diseases and other chronic diseases in comparison to noncarriers. In addition, the associations of this variant are different across various regions, ethnicities, and age groups.…”

Delayed intervention with a novel SGLT2 inhibitor NGI001 suppresses diet‐induced metabolic dysfunction and non‐alcoholic fatty liver disease in mice

“…A well‐known feature of metabolic syndrome is increase of lipid accumulation in the trunk region, which causes excessive visceral fat deposition (Mizuno, ). In order to confirm that the rising body weight gain was truly an increase of fat mass, we isolated the epididymal white adipose tissue from the mice.…”

The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

“…FTO polymorphisms are associated with high BMI and insulin resistance and may contribute to the development of NAFLD. Upregulation of FTO is consistently observed in clinical NAFLD patients as well as in rodent models, suggesting the potential implication of FTO in NAFLD [55,56].…”