Quantifying the contribution of “browned” white adipose tissue depots to whole-body glucose homeostasis (#54)
Recent studies have identified functional brown adipose tissue (BAT) in humans, as well as UCP1-positive adipocytes in white adipose tissue (WAT). This ‘browning’ of WAT occurs in response to cold exposure, or treatment with β3-adrenergic agonists or thiazolidinediones, and is thought to confer protection against diet-induced obesity and glucose intolerance. However, the contribution of browned WAT depots to whole-body energy expenditure and glucose homeostasis, independently of ‘classical’ BAT, has not been determined.
To study the effects of browning WAT depots, male C57BL6/J mice were fed either chow or a high-fat diet (HFD) for 4 weeks and then allocated to groups matched for adiposity and glucose tolerance. Mice received daily i.p. injections of either a browning agent (the selective β3-AR agonist BRL37344, 0.5 mg/kg) or saline for 2 weeks. A radiolabelled glucose tolerance test was performed prior to sacrifice.
Acute treatment with the browning agent increased energy expenditure (at thermoneutrality, 30°C) for ~4 hours. In HFD-fed mice but not in chow-fed mice, treatment with the browning agent improved glucose tolerance and reduced body weight, adiposity and insulinaemia relative to saline-treated mice (diet x treatment: P<0.05). Independently of diet, BRL37344 selectively reduced the mass of intra-abdominal fat pads (epididymal, retroperitoneal and mesenteric) (all P<0.05). As expected, UCP1 and PGC-1α protein content was increased in browned depots, particularly inguinal WAT, and oxygen consumption rate was increased in explants of WAT but not BAT. Glucose uptake was increased in browned retroperitoneal WAT, independently of diet; while in inguinal WAT, glucose uptake was increased by BRL37344 in chow-fed mice but reduced in HFD-fed mice (P=0.021). Glucose uptake in skeletal muscle and BAT was not affected by diet or BRL37344.
Browning WAT can resolve HFD-induced increases in adiposity and glycaemia in rodents. Future studies should also use lipid tracers (2-bromopalmitate) to assess substrate metabolism in browned WAT.