Irisin improves adiposity and exercise tolerance in a rat model of postmenopausal obesity through enhancing adipo-myocyte thermogenesis

Abstract

The prevalence of obesity and its associated metabolic disorders, along with their healthcare costs, is rising exponentially. Irisin, an adipomyokine, may serve as a critical cross-organ messenger, linking skeletal muscle with adipose tissue and the liver to integrate the energy homeostasis under diet-induced obesity. We aimed to explore the putative role of irisin in the protection against obesity in a postmenopausal rat model by modulating energy expenditure (EE). Bilateral ovariectomy (OVX) was performed. After 3 weeks of recovery, the OVX rats were classified according to their dietary protocol into rats maintained on normal diets (ND) (OVX) or high-fat diet (HFD) groups. The HFD-fed animals were equally divided into OVX/HFD, or irisin-treated OVX/HFD groups. Sham rats, maintained on ND, were selected as the control group. We evaluated anthropometric, EE, and molecular biomarkers of browning and thermogenesis in inguinal white adipose tissue and skeletal muscle, and the activity of the proteins related to mitochondrial long chain fatty acid transport, oxidation, and glycolysis. HFD of OVX further deteriorated the disturbed glucose homeostasis, lipid profile, and the reduced irisin, thermogenic parameters in adipose tissue and skeletal muscle, and EE. Irisin treatment improved the lipid profile and insulin resistance. That was associated with reduced hepatic gluconeogenic enzyme activities and restored hepatic glycogen content. Irisin reduced ectopic lipid infiltration. Irisin augmented EE by activating non-shivering thermogenesis in muscle and adipose tissues and decreasing metabolic efficiency. Our experimental evidence suggests irisin’s use as a potential thermogenic agent, therapeutically targeting obesity in postmenopausal patients. Graphical abstract Irisin modulates the non-shivering thermogenesis in skeletal muscle and adipose tissue in postmenopausal model

(-)-epicatechin treatment did not modify the thermogenic pathway in the gastrocnemius muscle of male rat offspring obeses by programming

“…Hence, it has been proposed that irisin modulates Sln, which can improve the function and thermogenesis of skeletal muscle. 42 In addition, in 2022, Son et al demonstrated in a mouse model of MO that the expression of sarcolipin and Ucp3 in skeletal muscle is decreased in offspring with diet-induced obesity and that this change is due to pathway regulation other than Find5/irisin. According to our results, we did not find that obesity by programming or Epi treatment modified the expression of Sln or Ucp3 in the offspring of 110 or 245 pnd; as mentioned for Fndc5/irisin or Pgc-1 α, the regulation of thermogenesis in skeletal muscle could occur through pathways other than Fndc5/irisin.…”

Irisin alleviated the reproductive endocrinal disorders of PCOS mice accompanied by changes in gut microbiota and metabolomic characteristics

“…Previous studies showed that mice were prone to insulin resistance by globally deleted irisin via CRISPR/Cas-9 and high-fat-diet (HFD) ( Wang et al, 2023 ). In addition, the insulin resistance of HFD-treated bilateral ovariectomy rats was reduced by irisin therapy ( Gheit et al, 2022 ). However, chronic voluntary wheel running exercise ameliorates metabolic index in HFD-induced obese C57BL6J mice, while no difference was found in serum irisin ( Cho et al, 2023 ).…”

The Participation of Irisin in the Mechanisms of Weight Loss in Obesity

“…It was associated with a decrease in the activity of gluconeogenic liver enzymes and restoration of liver glycogen content. Irisin reduces ectopic lipid inflation and increases energy expenditure by activating thermogenesis in muscle and adipose tissue and reducing metabolic efficiency [20].…”