The Effects of Glucagon-Like Peptide Type 1 (GLP-1) and its Analogues in Adipose Tissue: Is there a way to Thermogenesis?

Abstract

: Obesity is a global problem and the most common metabolic disorder leading to many associated diseases, such as arterial hypertensi on, ischemic heart disease, type 2 diabetes, certain types of cancer, impaired lipid and uric acid metabolism. The prevalence of obesity has risen globally in the past four decades in both children and adults, and it accounts for the rapid increase in the prevalence of diabetes. Currently, the study of thermogenic tissues, brown and beige adipose tissues, is of extreme value from the point of view of therapeutic potential for obesity and its associated diseases. An analogue of the glucagon-like peptide-1 (GLP-1) liraglutide, used in the treatment of type 2 diabetes, has been proven to have a positive effect on weight loss through appetite suppression. However, this mechanism of weight loss is not the only one involved. This article discusses the main molecular and cellular mechanisms of adipogenesis, as well as the effect of GLP-1 and its analogues, in particular liraglutide on this process through various transcription factors, signaling pathways and hormones, including brown and beige adipose tissue. Also the twincretins have had a positive effect on insulin resistance and fat beiging activation. The results of numerous studies have helped us to better understand the peripheral mechanisms of lipid metabolism regulation, and have demonstrated the effectiveness of GLP-1 analogues for the treatment of diabetes and obesity.

GLP‐1 analogs and regional adiposity: A systematic review and meta‐analysis

“…On the other hand, the meta‐regression analysis suggests that the magnitude of weight loss is not associated with adipose tissue quantity loss, implying that there may be direct effects of GLP‐1 analogs on adipose tissue. Indeed, pre‐clinical evidence has implicated GLP‐1 in improved insulin sensitivity, brown adipose tissue activation, and amelioration of adipose tissue inflammation 74 . Via these mechanisms, GLP‐1 analogs may directly influence adipogenesis, which could explain the effects on adipose tissue quantity.…”

“…Indeed, pre-clinical evidence has implicated GLP-1 in improved insulin sensitivity, brown adipose tissue activation, and amelioration of adipose tissue inflammation. 74 Via these mechanisms, GLP-1 analogs may directly influence adipogenesis, which could explain the effects on adipose tissue quantity.…”