http://news.yale.edu/2014/10/09/hun...m_medium=email&utm_campaign=ynalumni-10-14-14
Hunger Games: How the brain 'browns' fat to aid weight loss
By Karen N. Peart
October 9, 2014
Researchers at Yale School of Medicine have uncovered a molecular process in the brain known to control eating that transforms white fat into brown fat. This process impacts how much energy we burn and how much weight we can lose. The results are published in the Oct. 9 issue of the journal Cell.
Obesity is a rising global epidemic. Excess fatty tissue is a major risk factor for type 2 diabetes, cardiovascular disease, hypertension, neurological disorders, and cancer. People become overweight and obese when energy intake exceeds energy expenditure, and excess calories are stored in the adipose tissues. The adipose organ is made up of both white and brown fat. While white fat primarily stores energy as triglycerides, brown fat dissipates chemical energy as heat. The more brown fat you have, the more weight you can lose.
It has previously been shown that energy-storing white fat has the capacity to transform into energy-burning “brown-like” fat. In this new study, researchers from the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, demonstrate that neurons controlling hunger and appetite in the brain control the “browning” of white fat.
The publication can be found here (well, the abstract anyway - the whole article requires payment):
Cell. 2014 Oct 9;159(2):306-17. doi: 10.1016/j.cell.2014.09.010.
O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat.
Ruan HB1, Dietrich MO2, Liu ZW1, Zimmer MR3, Li MD4, Singh JP1, Zhang K4, Yin R1, Wu J1, Horvath TL5, Yang X6.
Author information
Abstract
Induction of beige cells causes the browning of white fat and improves energy metabolism. However, the central mechanism that controls adipose tissue browning and its physiological relevance are largely unknown. Here, we demonstrate that fasting and chemical-genetic activation of orexigenic AgRP neurons in the hypothalamus suppress the browning of white fat. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates fundamental cellular processes. The levels of O-GlcNAc transferase (OGT) and O-GlcNAc modification are enriched in AgRP neurons and are elevated by fasting. Genetic ablation of OGT in AgRP neurons inhibits neuronal excitability through the voltage-dependent potassium channel, promotes white adipose tissue browning, and protects mice against diet-induced obesity and insulin resistance. These data reveal adipose tissue browning as a highly dynamic physiological process under central control, in which O-GlcNAc signaling in AgRP neurons is essential for suppressing thermogenesis to conserve energy in response to fasting.
Ever since I learned about the difference between brown and white fat in grad school, I have hypothesized that a mechanism that increased my brown fat (which "wastes" fat to produce heat, and thus is important to keep babies and hibernating animals alive) would result my being warm and thin, rather than fat and cold (white fat stores and vigorously hangs on to fat to protect us from starvation). If it is possible to convert white fat to brown, this would be fantastic! Of course, and unfortunately, any means of doing so is a very very long way off .... but this research is a start - by understanding the pathway, perhaps rational drug design might be able to develop a medication that replicates the normal process.
Hunger Games: How the brain 'browns' fat to aid weight loss
By Karen N. Peart
October 9, 2014
Researchers at Yale School of Medicine have uncovered a molecular process in the brain known to control eating that transforms white fat into brown fat. This process impacts how much energy we burn and how much weight we can lose. The results are published in the Oct. 9 issue of the journal Cell.
Obesity is a rising global epidemic. Excess fatty tissue is a major risk factor for type 2 diabetes, cardiovascular disease, hypertension, neurological disorders, and cancer. People become overweight and obese when energy intake exceeds energy expenditure, and excess calories are stored in the adipose tissues. The adipose organ is made up of both white and brown fat. While white fat primarily stores energy as triglycerides, brown fat dissipates chemical energy as heat. The more brown fat you have, the more weight you can lose.
It has previously been shown that energy-storing white fat has the capacity to transform into energy-burning “brown-like” fat. In this new study, researchers from the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, demonstrate that neurons controlling hunger and appetite in the brain control the “browning” of white fat.
The publication can be found here (well, the abstract anyway - the whole article requires payment):
Cell. 2014 Oct 9;159(2):306-17. doi: 10.1016/j.cell.2014.09.010.
O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat.
Ruan HB1, Dietrich MO2, Liu ZW1, Zimmer MR3, Li MD4, Singh JP1, Zhang K4, Yin R1, Wu J1, Horvath TL5, Yang X6.
Author information
Abstract
Induction of beige cells causes the browning of white fat and improves energy metabolism. However, the central mechanism that controls adipose tissue browning and its physiological relevance are largely unknown. Here, we demonstrate that fasting and chemical-genetic activation of orexigenic AgRP neurons in the hypothalamus suppress the browning of white fat. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates fundamental cellular processes. The levels of O-GlcNAc transferase (OGT) and O-GlcNAc modification are enriched in AgRP neurons and are elevated by fasting. Genetic ablation of OGT in AgRP neurons inhibits neuronal excitability through the voltage-dependent potassium channel, promotes white adipose tissue browning, and protects mice against diet-induced obesity and insulin resistance. These data reveal adipose tissue browning as a highly dynamic physiological process under central control, in which O-GlcNAc signaling in AgRP neurons is essential for suppressing thermogenesis to conserve energy in response to fasting.
Ever since I learned about the difference between brown and white fat in grad school, I have hypothesized that a mechanism that increased my brown fat (which "wastes" fat to produce heat, and thus is important to keep babies and hibernating animals alive) would result my being warm and thin, rather than fat and cold (white fat stores and vigorously hangs on to fat to protect us from starvation). If it is possible to convert white fat to brown, this would be fantastic! Of course, and unfortunately, any means of doing so is a very very long way off .... but this research is a start - by understanding the pathway, perhaps rational drug design might be able to develop a medication that replicates the normal process.
