Hyperthermia Treatment Attenuates Diet-Induced Obesity and Insulin Resistance in Older Female and Ovariectomized Mice via TRPV1-Mediated Futile Calcium Cycling

Presenter

Sean Tobin Bannon

Campus

UMass Amherst

Sponsor

Soonkyu Chung, Department of Nutrition, UMass Amherst

Schedule

Session 1, 10:30 AM - 11:15 AM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board C21, Poster Showcase Room (163), Row 3 (C21-C30) [Poster Location Map]

Abstract

Objectives: Menopause is associated with deregulated metabolism and an increased risk of obesity. Heat treatment (HT) is an emerging therapeutic that has been shown to exert metabolic benefits partially mimicking physical activity. However, the impact of HT on aging and menopause-associated obesity and its associated metabolic dysfunction remains elusive. This study aims to investigate the impact of HT on attenuating obesity and metabolic dysfunction in old female mice and elucidate the underlying molecular mechanisms.

Methods: Ten-month-old female C57BL/6 mice and ovariectomized (OVX) mice were utilized to model aging and post-menopausal conditions, respectively. Mice were fed a Western diet with or without daily HT for 30 minutes for 12 weeks. Effects of HT on body composition, weight gain, insulin sensitivity, blood lipids, glucose profiles, and metabolic adaptation were assessed, including core body temperature and lipid metabolism transcription levels in adipose tissue and liver. Human white and brown adipocytes were used to confirm the metabolic impact of HT. 

Results: Whole body HT improved insulin sensitivity and AKT signaling, and reduced diet-induced weight gain and lipid accumulation while increased fatty acid beta-oxidation genes in the liver and brown fat. The elevated expression of transient receptor potential vanilloid 1 (TRPV1) and genes associated with Ca2+/ATP-pump on the plasma membrane and ER suggests that HT triggers ATP-consuming futile calcium cycling. These findings were confirmed in human brown and white adipocytes.

Conclusions: Whole-body heat therapy effectively reduces aging and menopause-associated obesity and insulin resistance by activating TRPV1, inducing futile calcium cycling, and promoting thermogenic energy expenditure.

Keywords

Heat Treatment, Aging, Post-menopausal Obesity, n-3 PUFA, Energy Expenditure

Research Area

Public Health and Epidemiology

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