Brown fat transplantation improves obesity and glucose metabolismLiu X et al., Endocrinology. 2015
Brown adipose tissue transplantation reverses obesity in Ob/Ob mice.
Liu X, Wang S, You Y et al.
Endocrinology. 2015 Apr 1:en20141598. [Epub ahead of print]
BackgroundIn addition to white adipose tissue (WAT), humans and small mammals also have brown adipose tissue (BAT) and brown in white (brite or beige) adipose depots [1,2]. Visceral and subcutaneous (SUB) WAT also differ in physiology; SUB adipocytes are larger than visceral adipocytes  and SUB fat contain more mitochondria .
Recent findings suggest that weight loss may be achieved by increasing energy expenditure through activation of BAT . Transplantation of BAT (trBAT) to type I diabetes mice reversed clinical symptoms (hyperglycaemia, loss of adiposity and polyphagia), suggesting a role for adipokines from trBAT in glycaemic control . BAT transplantation has also been shown to improve energy expenditure and glucose homeostasis [7-8] and to reverse high-fat diet (HFD) induced obesity and pre-existing obesity .
Leptin-deficient Ob/Ob mice are a model for studying obesity-induced diabetes, because of their metabolic phenotype resembling diabetes, including hyperphagia, glucose intolerance and adipocyte hyperplasia. As a consequence of BAT dysfunction, these mice have a lower metabolic rate and hypothermia [9-10]. This study explored whether BAT has benefits in genetically obese Ob/Ob mice, via BAT transplantation from wild type mice, into the dorsal SUB region of Ob/Ob mice (6 weeks old).
- BAT-transplanted Ob/Ob mice gained more weight than sham-operated control Ob/Ob mice, already 3 weeks after the transplantation. BAT-transplanted mice had 11% less whole body fat than control mice. SUB adipose tissue, but not epididymal, endogenous BAT or liver tissue was decreased after trBAT.
- TrBAT completely reversed the hepatic steatosis normally seen in Ob/Ob mice. Gene expression of PPARγ2 and TNFα in the liver was lower, and of PGC1α, which induces genes that regulate hepatic fatty acid metabolism, was increased, while the expression of other genes involved in fatty acid metabolism was not changed.
Hepatic triglycerides (TG) content and circulating TG, cholesterol and LDL were significantly lower after BAT transplantation.
- A glucose tolerance test showed that BAT transplantation improved insulin sensitivity.
- Indirect calorimetry showed that oxygen consumption was significantly higher in BAT-transplanted mice, with unchanged energy intake. BAT transplantation also led to higher physical activity.
- Expression of genes related to mitochondrial biogenesis and thermogenesis were remarkably increased in endogenous BAT, but not in epididymal or SUB fat after trBAT. Also expression of other genes and mitochondrial proteins suggest enhanced endogenous BAT activity.
- Results indicate that trBAT lost some of its molecular characteristics, thus that it is most likely the activation of endogenous BAT, possibly via adiponectin, rather than metabolic activity of trBAT itself that changes whole body energy metabolism.
ConclusionAs an endocrine organ, BAT receives interest as a potential new therapeutic target for obesity and related diseases. Specifically, stimulating the activity of BAT and/or increasing the amount of BAT for the prevention and treatment of obesity and metabolic syndrome is topic of research. This study showed that transplantation of BAT ameliorated body weight and body fat gain in leptin-deficient obese mice. BAT transplantation increased activity of endogenous BAT, thereby improving whole body energy metabolism, and glucose homeostasis. In addition to improved energy expenditure and thermogenic capacity, fatty acid oxidation related gene expression also increased in endogenous BAT.
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