Effects of Elevated Hypothalamic Inflammation on Obesity and Feeding

Tien-Jui Lee, Purdue University

Abstract

It has been demonstrated that Western diet consumption induces chronic mild inflammation in the hypothalamus. However, whether hypothalamic inflammation influences feeding or obesity development remains unclear. This research examined if peripheral inflammation, weight gain, or elevated adiposity caused diet-induced hypothalamic inflammation in male Sprague Dawley rat model. Rats fed with Western diet (HFHS) or high-fat low-carbohydrate ketogenic diet (Keto) had higher fat mass and hypothalamic inflammation after 10, 40, or 90 days compared to chow-fed animals. However, only HFHS rats had higher calorie intake in the first week and higher body weight gain after 40 days. Plasma cytokines were only higher in Keto rats at day 10, and no differences in adipose cytokines among groups were found. In another study, rats fed with high-fat diet (HFD) slightly increased microglia in the arcuate nucleus (Arc) on day 1 and also gradually increased TNFα expression in the peri-Arc area. However, no significant changes of hypothalamic TNFα and NFκB mRNA expression were found. This research also hypothesized that elevated proinflammatory cytokines in the brain influenced energy balance or peripheral lipid metabolism. Rats received daily intracerebrovantricular (i.c.v.) injection of 0.5 pg TNFαfor 6 days had significantly higher average daily food intake than saline-injected rats. Rats with continuously i.c.v. infusion of 0.5 pg TNFα 26 days had lower hepatic fatty acid synthase (FAS) and the epididymal adipose sterol regulatory element-binding protein 1c (SREBP-1c) than saline-infused rats without any differences in body weight change, food intake, fat mass, lean mass, plasma glucose. HFD-fed rats with 4-day daily i.c.v. a NFκB inhibitor, NEMO-binding domain peptide (NBD), had higher food intake on the second day than rats received saline injection. However, there were no significant differences in inflammatory genes expression in the hypothalamus between the two groups. Collectively, these data suggest that fat content in the diet may be the main trigger of diet-induced neuroinflammation. The inflammatory response includes more microglia activation and higher cytokines, that is independent of body weight gain, calorie intake, and peripheral inflammation. Elevated neuroinflammaion may have an acute effect on food intake and favor fat storage in the long term. These findings improve our understanding of the role of brain inflammation on adiposity and some possible mechanisms of energy balance.

Degree

Ph.D.

Advisors

Kinzig, Purdue University.

Subject Area

Nutrition|Psychology

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