In a finding that may challenge popular notions of body fat and health, researchers at Beth Israel Deaconess Medical Center (BIDMC) have shown how fat cells can protect the body against diabetes.
The results may lead to a new therapeutic strategy for preventing and treating type 2 diabetes and obesity-related metabolic diseases, the authors say.
In the last decade, several research groups have shown that fat cells in people play a major role in controlling healthy blood sugar and insulin levels throughout the body. To do this crucial job, fat cells need a small portion of the sugars derived from food. Obesity often reduces the dedicated sugar transport molecules on fat cells, blocking the glucose from entering fat cells. As a result, the whole body becomes insulin resistant, and blood sugar rises, leading to diabetes.
The new study shows why glucose is so important to fat cells. The team discovered a new version of a gene inside fat cells that responds to sugar with a powerful systemic effect.
“If we change that one gene, that makes the animal more prone to or more protected from diabetes,” said senior author Barbara Kahn MD, the George R. Minot Professor of Medicine at Harvard Medical School and Vice Chair of the Department of Medicine at BIDMC. “Many foods get converted into sugar, so there is no need to eat more sugar.”
The paper is published online April 1 in the journal Nature. In the study, the BIDMC researchers pinpointed the fat gene and its effect in mouse models of human obesity and insulin resistance and reported supporting evidence from fat tissue samples from both lean and obese people.
“Two things were surprising – first, that a lone gene could shift the metabolism of the fat cell so dramatically and then, that turning on this master switch selectively in adipose tissue is beneficial to the whole body,” Kahn said. Twelve years ago, Kahn first demonstrated that fat cells are a master regulator of healthy levels of glucose and insulin in mice and require sugar to do the job.
In the latest study, evidence suggests the newfound gene also may account for the protective effect of glucose uptake in human fat. German collaborators found more gene activity in people with greater insulin sensitivity, based on 123 adipose tissue samples from non-diabetic, glucose tolerant people. The fat gene activity also correlated highly with insulin sensitivity in obese, non-diabetic people, as measured in 38 fat samples by another pair of co-authors based in St. Louis.
In fat cells, the newfound gene acts as a glucose sensor that converts the sugars into fatty acids, which may play a role in the powerful systemic effect. In response to rising glucose levels, the gene makes a more active version of itself. The active version turns on the cellular machinery that disassembles the sugar molecules and remakes them into fatty acids. The novel version of this gene is called carbohydrate-responsive-element-binding protein-beta, or ChREBP-beta for short.