(P16-007-23) Fish Oil and Heat Treatment Induce Metabolic Benefits Against Post-Menopausal Obesity via the Activation of HSP70/TRPV1 Axis and Modulation of Endocannabinoid System

Objectives: Postmenopausal obesity is associated with dysregulated metabolism and notably, the decline in energy expenditure. Heat treatment (HT) is an emerging practice that exhibits metabolic benefits mimicking exercise. Previously, we have shown that fish oil (FO) supplementation is a potent dietary factor to promote thermogenic energy expenditure. This study aimed to evaluate whether HT with FO intake exerts a synergistic effect in promoting energy expenditure, overriding the metabolic slowdown due to aging and menopause.

Methods: 10-month-old female C57BL6 mice were given isocaloric high-fat (HF) diet (45% calories from fat) with or without fish oil. Mice were challenged with daily exposure to heat (40 ℃) for 30 min for 12 weeks. Body composition and metabolic adaptation were assessed by EchoMRI and core body temperature. Metabolic factors including glucose and insulin tolerance and lipid profiles were measured. Activation of brown thermogenesis was assessed by measuring brown-signature gene expressions and thermogenic heat release. To investigate the molecular interactions with heat and fish oil, we utilized immortalized human brown and white adipocytes in the combination of chemical or thermal activation of transient receptor potential vanilloid 1(TRPV1) and omega-3 polyunsaturated fatty acid (n-3 PUFA) treatment.

Results: FO intake with HT significantly attenuated the HF diet-induced weight gain and improved insulin sensitivity. More importantly, HT and FO exerted a synergistic effect on enhancing energy expenditure via 1) the co-activation of TRPV1 and heat shock protein 70 (HSP70), 2) augmented adipocyte beiging in inguinal white adipose tissue (iWAT) as well as brown adipose tissue (BAT), and 3) modulated endocannabinoid (ECB) system in iWAT and BAT. Our in vitro results revealed that concomitant activation of TRPV1, either by heat or agonist, and n-3 PUFA accelerated brown adipogenesis in human brown adipocytes. Inversely, inhibition of TRPV1 attenuated the HT and n-3 PUFA-mediated thermogenic energy expenditure, suggesting that TRPV1 activation is required for HT and n-3 PUFA-induced thermogenic activation.

Conclusions: Our results suggested that HT and n-3 PUFA intake synergistically improved the metabolic slowdown and protected against post-menopausal obesity via enhancement of brown thermogenic activity.

Funding Sources: UMass Amherst