Heat Therapy Decreases Adipose Tissue Inflammation and Improves Insulin Signaling in Polycystic Ovary Syndrome

Abstract

Passive hot water immersion promotes improvements in glucose control in humans, potentially by enhancing insulin sensitivity. In animal models, this improvement is mediated by increased heat shock protein (HSP) abundance, which inhibits production of inflammatory compounds that interfere with intracellular insulin signaling. The impact of repeated passive hot water immersion (termed ‘heat therapy’) on inflammation, HSP abundance, and insulin signaling in human adipose tissue have not been explored in an insulin‐resistant population such as obese women with Polycystic Ovary Syndrome (PCOS). While exercise training can improve insulin sensitivity in PCOS, novel treatments such as heat therapy are warranted as many individuals are unable to fully benefit from a traditional exercise program due to poor exercise tolerance or capacity. Therefore, the objective of this study was to examine changes in insulin signaling, inflammatory proteins, and HSPs in subcutaneous adipose tissue of obese women with PCOS undergoing an 8–10 week heat therapy intervention. Six obese women with PCOS (Age: 26±3y, BMI 42±2 kg·m2) underwent heat therapy, consisting of 30 × 1‐hr hot tub sessions over 8–10 weeks (3–4 per week) in 40.5°C water. Subcutaneous adipose tissue biopsies were collected from the periumbilical region at the start (Pre) and end (Post) of the chronic heat intervention. Tissue samples were analyzed using immunoblotting for HSP27, HSP70, and inflammatory proteins known to be impacted by HSPs and interfere with insulin signaling, including c‐Jun‐NH2‐terminal Kinase (JNK; inhibited by HSP70) and Inhibitor of Kappa B Kinase β (IKKβ; inhibited by HSP27). Additionally, a sub‐set of primary adipocytes in n=4 subjects were serum starved for 2 hours, then exposed to 1.2 nM insulin for 5 minutes for insulin signaling (p‐AKT) analysis using immunoblotting. All targets were quantified relative to loading control and expressed as a fold change from Pre to Post. Following heat therapy, insulin signaling (p‐AKT) increased in all subjects (4.1±2.0‐fold increase, p=0.19) despite no change in BMI (p=0.42). IKKβ significantly decreased (0.50 ± 0.06‐fold decrease, p=0.02) and JNK tended to decrease (0.48 ± 0.17‐fold decrease, p=0.09) after heat therapy. Abundance of HSP27 increased in all subjects (1.27 ± 0.14‐fold increase, p=0.18), while, conversely, HSP70 abundance significantly decreased (0.42±0.12‐fold decrease; p=0.03). In these preliminary data, heat therapy appears to promote improved insulin signaling in obese women with PCOS. This improvement is likely due to observed decreases in adipose tissue inflammation, potentially mediated in part by increased HSP27 abundance. Regular heat exposure has promise as a novel treatment in insulin‐resistant individuals to improve metabolic function. Heat can potentially be implemented as a complement or as a transition to exercise training to improve metabolic health, particularly in patient populations with severe metabolic dysfunction, mobility limitations, or low exercise tolerance.Support or Funding InformationSupported by American Heart Association Predoctoral Fellowship 16PRE27780085, Eugene & Clarissa Evonuk Memorial Fellowship, and the Ken and Kenda Singer Endowment Fund.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.