Browning of white fat: agents and implications for beige adipose tissue to type 2 diabetes

Abstract

Mammalian adipose tissue is traditionally categorized into white and brown relating to their function and morphology: while white serves as an energy storage, brown adipose tissue acts as the heat generator maintaining the core body temperature. The most recently identified type of fat, beige adipocyte tissue, resembles brown fat by morphology and function but is developmentally more related to white. The synthesis of beige fat, so-called browning of white fat, has developed into a topical issue in diabetes and metabolism research. This is due to its favorable effect on whole-body energy metabolism and the fact that it can be recruited during adult life. Indeed, brown and beige adipose tissues have been demonstrated to play a role in glucose homeostasis, insulin sensitivity, and lipid metabolism—all factors related to pathogenesis of type 2 diabetes. Many agents capable of initiating browning have been identified so far and tested widely in humans and animal models including in vitro and in vivo experiments. Interestingly, several agents demonstrated to have browning activity are in fact secreted as adipokines from brown and beige fat tissue, suggesting a physiological relevance both in beige adipocyte recruitment processes and in maintenance of metabolic homeostasis. The newest findings on agents driving beige fat recruitment, their mechanisms, and implications on type 2 diabetes are discussed in this review.

Dynamic contrast‐enhanced MRI of brown and beige adipose tissues

“…The group 2 animals from cohort I ( n = 7) were treated with saline; and group 3 from cohort I ( n = 7) were treated with the β3‐adrenergic receptor agonist CL‐316,243 (1 mg/kg body weight of the animal) by intraperitoneal route for 3 days. The CL‐316,243 is a β3‐adrenergic receptor agonist that can activate BAT and also has been used to convert WAT into beige adipose tissues . The iBAT tissue was validated by analysis of functional molecular markers UCP1, VEGF, and CPT1.…”

“…The CL-316,243 is a β3-adrenergic receptor agonist that can activate BAT 48 and also has been used to convert WAT into beige adipose tissues. 42 The iBAT tissue was validated by analysis of functional molecular markers UCP1, VEGF, and CPT1.…”

“…The iBAT is located in the interscapular region of the rat. Earlier work has shown that beige adipose tissue can be created in the inguinal region, by trans‐differentiation of the WAT . The feasibility of browning the WAT has been demonstrated by biochemical and transcriptomic studies in cells and rodents .…”

“…Earlier work has shown that beige adipose tissue can be created in the inguinal region, by trans-differentiation of the WAT. 14,[41][42][43] The feasibility of browning the WAT has been demonstrated by biochemical and transcriptomic studies in cells 44,45 and rodents. 20,46,47 However, there is lack of noninvasive imaging methods for identifying and evaluating the browning process.…”

Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenic response in subcutaneous adipose tissue

“…When activated, thermogenesis promotes metabolic flexibility mainly catabolizing glucose and fats with a beneficial impact on overall body metabolism (Harms and Seale, 2013). Impinging thermogenesis in WAT to overwhelm metabolic diseases is an emerging and promising field of research (Kaisanlahti and Glumoff, 2019). A strategy to activate thermogenesis in WAT could be exercise or cold exposure, but it would seem difficult to apply this condition in daily life in human.…”