Researchers Uncover Molecular Process in the Brain that Transforms White Fat into Brown Fat

Yale researchers reveal the transformation of white fat into brown fat by a brain-controlled molecular process, impacting how much energy we burn and how much weight we can lose. Credit: Michael S. Helfenbein

Yale scientists uncover how a molecular process in the brain that is known to control eating transforms white fat into brown fat, impacting how much energy we burn and how much weight we can lose.

The results are published in the October 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.

Lead author Xiaoyong Yang, associate professor of comparative medicine and physiology at Yale School of Medicine, conducted the study with Tamas Horvath, professor and chair of comparative medicine, and professor of neurobiology and Obstetrics/gynecology at Yale School of Medicine, and their co-authors.

The team stimulated this browning process in the brain of mice and found that it protected the animals from becoming obese on a high-fat diet. The team then studied the molecular changes in hunger-promoting neurons in the hypothalamus and found that the attachment of a unique sugar called “O-GlcNAc” to potassium ion channels acts as a switch to control brain activity to burn fat.

“Our studies reveal white fat “browning” as a highly dynamic physiological process that the brain controls,” said Yang. “This work indicates that behavioral modifications promoted by the brain could influence how the amount of food we eat and store in fat is burned.”

Yang said hunger and cold exposure are two life-history variables during the development and evolution of mammals. “We observed that food deprivation dominates over cold exposure in neural control of white fat browning. This regulatory system may be evolutionarily important as it can reduce heat production to maintain energy balance when we are hungry. Modulating this brain-to-fat connection represents a potential novel strategy to combat obesity and associated illnesses.”

Other authors on the study include Hai-Bin Ruan, Marcelo O. Dietrich, Zhong-Wu Liu, Marcelo R. Zimmer, Min-Dian Li, Jay Prakash Singh, Kaisi Zhang, Ruonan Yin, and Jing Wu.

The study was funded by the National Institutes of Health, American Diabetes Association, Ellison Medical Foundation, American Heart Association, and CNPq/Brazil.

Reference: “O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat” by Hai-Bin Ruan, Marcelo O. Dietrich, Zhong-Wu Liu, Marcelo R. Zimmer, Min-Dian Li, Jay Prakash Singh, Kaisi Zhang, Ruonan Yin, Jing Wu, Tamas L. Horvath and Xiaoyong Yang, 9 October 2014, Cell.
DOI: 10.1016/j.cell.2014.09.010