Physical Exercise Enhanced Heat Shock Protein 60 Expression and Attenuated Inflammation in the Adipose Tissue of Human Diabetic Obese

Abstract

Heat shock protein 60 (HSP60) is a key protein in the crosstalk between cellular stress and inflammation. However, the status of HSP60 in diabetes and obesity is unclear. In the present study, we investigated the hypothesis that HSP60 expression levels in the adipose tissue of human obese adults with and without diabetes are different and physical exercise might affect these levels. Subcutaneous adipose tissue (SAT) and blood samples were collected from obese adults with and without diabetes (n = 138 and n = 92, respectively, at baseline; n = 43 for both groups after 3 months of physical exercise). Conventional RT-PCR, immunohistochemistry, immunofluorescence, and ELISA were used to assess the expression and secretion of HSP60. Compared with obese adults without diabetes, HSP60 mRNA and protein levels were decreased in SAT in diabetic obese together with increased inflammatory marker expression and glycemic levels but lower VO2 Max. More interestingly, a 3-month physical exercise differentially affected HSP60 expression and the heat shock response but attenuated inflammation in both groups, as reflected by decreased endogenous levels of IL-6 and TNF-α. Indeed, HSP60 expression levels in SAT were significantly increased by exercise in the diabetes group, whereas they were decreased in the non-diabetes group. These results were further confirmed using immunofluorescence microscopy and anti-HSP60 antibody in SAT. Exercise had only marginal effects on HSP60 secretion and HSP60 autoantibody levels in plasma in both obese with and without diabetes. Physical exercise differentially alleviates cellular stress in obese adults with and without diabetes despite concomitant attenuation of the inflammatory response.

Soluble Epoxide Hydrolase 2 Expression Is Elevated in Obese Humans and Decreased by Physical Activity

“…The only study focusing on EPHX2 modulation by exercise was reported in mice and showed decreased EPHX2 expression only in the kidney [40]. We and others have previously reported the beneficial effects of regular exercise in obese individuals [17,41,42]. Here, our exercising obese group showed increased maximal oxygen consumption along with improvements in the metabolic markers HDL, TG, glycemia, and stress response chaperones (GRP78 and HSP72), suggesting that the effects of our exercise protocol were global despite the negligible weight decrease and absence of a specific prescribed diet.…”

Interplay between diet, exercise and the molecular circadian clock in orchestrating metabolic adaptations of adipose tissue

“…Nevertheless, emerging data suggests that the adipose tissue-specific adaptation to exercise may be partly defective in obese insulin-resistant individuals. For example, the angiogenic response to aerobic exercise is blunted, concomitant with reduced adrenergically induced lipolysis in subcutaneous adipose tissue (Walton et al 2015;Verboven et al 2018), while the beneficial effect on inflammation is maintained (Khadir et al 2018).…”

<p>The Exercise Training Modulatory Effects on the Obesity-Induced Immunometabolic Dysfunctions</p>

“…175 Although the serum levels of HSP60 have increased following a 3-month aerobic exercise, a significant reduction is shown in individuals with obesity and diabetes. 181 The potential impacts of exercise training on the immune system are also found by increasing the serum level of adiponectin and IL-10 in OW/OB women after water running. 192 In addition to increased adiponectin serum concentration, the IL-15 levels have increased following a 24-week combined exercise in adult men with obesity.…”

“…176 Participating in a 3-month moderate aerobic exercise training has been reported to upregulate HSP60, IL-6, and TNFα among people with obesity and T2D. 181 However, reduction of HSp60 and HSP70, higher IL-10, and unchanged values of TNFα mRNA expression have been reported following 8-week resistance training in elder healthy subjects. 13 In this state, a significant reduction of TNFα protein levels is found following a whole-body vibration in dynamic or static exercise among elder subjects with OW.…”