Hypothalamic Gliosis May Be Associated With Insulin Resistance, Obesity

There may be a strong link between hypothalamic gliosis and insulin resistance, independent of adiposity, in humans, according to a recent study.

The results, which were presented at ObesityWeek 2015, were based on radiologic evidence.

“The purpose of the study was to use (magnetic resonance imaging [MRI]) to look for evidence of structural changes in the human hypothalamus and test whether these changes were related to obesity or insulin resistance,” said lead study investigator Ellen Schur, MD, who is with the University of Washington in Seattle. 

“We found evidence for gliosis in the mediobasal region of the hypothalamus that encompasses the arcuate nucleus, a critical hypothalamic structure regulating both energy and glucose homeostasis. Gliosis is the brain’s response to inflammation and neuron injury.”

Dr Schur said animal models have suggested that diet-induced obesity is associated with inflammation and gliosis within the hypothalamus. However, this study reported at ObesityWeek is the first prospective report on detection of gliosis in the human hypothalamus both in vivo and in postmortem samples. 

She noted that MRI appears to be useful for investigating the role of mediobasal hypothalamic gliosis in the pathogenesis and maintenance of human obesity. This study also may be clinically relevant because it may point to new avenues of prevention, she added. 

Dr Schur and colleagues used quantitative MRI to test whether mediobasal hypothalamic gliosis was associated with obesity and insulin resistance in 67 participants who underwent a fasting blood draw and MRI. The researchers applied a quantitative MRI technique to measure T2 relaxation time in the mediobasal hypothalamus.

In this study, radiologic evidence of mediobasal hypothalamic gliosis (n=22) was identified as the upper tertile of left mediobasal hypothalamic T2 relaxation time and was compared with controls (n=23) from the lowest tertile.

The investigators then conducted a separate autopsy study in which brain slices (n=10) through the mediobasal hypothalamus were imaged by MRI and stained for glial fibrillary acidic protein (GFAP). 

The study demonstrated that longer T2 relaxation time in the left mediobasal hypothalamus was associated with higher BMI in all participants. The researchers also found that the cases had longer T2 relaxation times in the right mediobasal hypothalamus, and had higher BMIs, fasting insulin concentrations, and homeostatic model assessment- insulin resistance (HOMA-IR) values, as compared with controls when adjusted for sex and age.

The elevations in insulin and HOMA-IR were also independent of BMI, according to the data.

“There is a growing literature pointing to an important role for the brain in regulating glucose homeostasis. Our findings show evidence of inflammation and scarring in a critical glucose-regulating brain area in humans,” Dr Schur told Endocrinology Advisor.

“While further study is needed, practitioners should know that these new data suggest that structural changes in the hypothalamus are present in obesity and insulin resistance. Clinically, these data further support a disease model of obesity in which potentially both central processing of energy and glucose homeostasis are affected.”

She said clinicians should consider obesity a chronic disease and watch for more studies regarding the role of the brain in the progression to insulin resistance and diabetes. 

Dr Schur and her team believe that future studies should employ more quantitative tools to investigate changes in glucose metabolism and insulin action associated with mediobasal hypothalamic gliosis.

They noted that further studies are warranted, including those on distinguishing whether switching from a high-fat to a low-fat diet is beneficial as well as studies investigating what role weight loss may play.

Reference

1. Schur E. Obesity Journal Symposium. Radiologic Evidence that Hypothalamic Gliosis is Associated with Obesity and Insulin Resistance in Humans. Presented at ObesityWeek; November 2-6, 2015; Los Angeles, CA.
2. Schur EA, Melhorn SJ, Oh S-K, et al. Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans. Obesity. 2015;23(11):2142-2148.