The biggest obstacle to the successful treatment of obesity is the tendency to regain weight lost through diet and exercise, and evidence is increasing that this could be due to physiological causes. Recently, an Australian study reported that after large weight loss, appetite-regulating hormones appear to reset to levels that increase appetite.

Now a new study reported online on 27 December in the Journal of Clinical Investigation, offers further evidence. Senior author Dr. Michael W. Schwartz, professor of medicine at the University of Washington, and colleagues, report how rodents and humans with diet-induced obesity have structural changes in an area of the brain that regulates weight control.

The hypothalamus is a small, pearl-sized area of the brain that controls a large number of body functions, including body weight, which is regulated by a complex set of interactions between hormones and neurons or brain cells. There is a growing belief among scientists that these interactions, in most obese people, “conspire” to prevent permanent weight loss, and the underlying mechanisms are increasingly becoming the object of intense investigation by neuroendocrinologists.

Schwartz told the press:

“To explain a biologically elevated body weight ‘set-point’, investigators in the field have speculated about the existence of fundamental changes to brain neurocircuits that control energy balance. Our findings are the first to offer direct evidence of such a structural change, and they include evidence in humans as well as in mice and rats.”

Schwartz and colleagues looked at what high-fat diets did to the brains of mice and rats engineered to become obese on such diets.

They found that quite early in their lives, the rodents developed lasting brain injuries in a specific part of the hypothalamus (the hypothalamic arcuate nucleus). Using brain scans, they found similar injuries in the same area of the brain of obese humans:

“Consistent with these data in rodents, we found evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI,” they write.

Schwartz, who holds the Robert H. Williams Endowed Chair in Medicine in the Division of Metabolism, Endocrinology and Nutrition, pointed out that these findings do not prove a cause and effect: that is they can’t say for sure that the brain injury is the reason the body appears to defend a higher body weight, that has yet to be proved, but:

“… this amounts to solid evidence of a change affecting the key hypothalamic area for body weight control with the potential to explain the problem,” he added.

In another study in the same issue of the journal, a second team of researchers, led by senior author Dr Jeffrey Flier, of Beth Israel Deaconess Medical Center, Boston, reports finding that turnover of nerve cells in the hypothalamus of mice is inhibited by obesity, adding further weight to the argument that physiology, rather than lapsing back to old eating habits, could be the reason for weight regain following a period of successful weight loss in obese people.

Written by Catharine Paddock PhD