Exercise retards ongoing adipose tissue fibrosis in diet-induced obese mice

Abstract

Exercise has been recommended as an important strategy to improve glucose metabolism in obesity. Adipose tissue fibrosis is associated with inflammation and is implicated in glucose metabolism disturbance and insulin resistance in obesity. However, the effect of exercise on the progression of adipose tissue fibrosis is still unknown. The aim of the present study was to investigate whether exercise retarded the progression of adipose tissue fibrosis and ameliorated glucose homeostasis in diet-induced obese mice. To do so, obesity and adipose tissue fibrosis in mice were induced by high-fat diet feeding for 12 weeks and the mice subsequently received high-fat diet and exercise intervention for another 12 weeks. Exercise alleviated high-fat diet-induced glucose intolerance and insulin resistance. Continued high-fat diet feeding exacerbated collagen deposition and further increased fibrosis-related gene expression in adipose tissue. Exercise attenuated or reversed these changes. Additionally, PPARγ, which has been shown to inhibit adipose tissue fibrosis, was observed to be increased following exercise. Moreover, exercise decreased the expression of HIF-1α in adipose fibrosis, and adipose tissue inflammation was inhibited. In conclusion, our data indicate that exercise attenuates and even reverses the progression of adipose tissue fibrosis, providing a plausible mechanism for its beneficial effects on glucose metabolism in obesity.

Adipose Tissue Extracellular Matrix Remodeling in Response to Dietary Patterns and Exercise: Molecular Landscape, Mechanistic Insights, and Therapeutic Approaches

“…More recently, Li et al [7] provided plausible mechanisms for the beneficial effects of exercise on adipose tissue fibrosis in obesity. Aerobic exercise training (50 min/day at 75% maximum oxygen consumption, 5 times/week for 12 weeks) attenuated the increased fibrosis-related gene expression (Col3α1, Col6α1, Lox, and Fibronectin) in epididymal adipose tissue of mice exposed to HFD for 12 weeks.…”

“…PPARγ activation following exercise has been proven to downregulate HIF-1α expression and reduce adipose tissue collagen deposition, which is essential for retarding ongoing adipose tissue fibrosis [7]. Furthermore, PPARγ agonist treatment primes monocytes into anti-inflammatory M2 macrophages and reduces proinflammatory cytokine expression [105].…”

“…ECM is formed principally in adipose tissue by collagens (I, VII), fibronectin, elastin, glycosaminoglycan (GAG), and a small quantity of laminin [5][6][7][8]. ECM remodeling is necessary to provide enough space for adipocyte hypertrophy and precursor cell hyperplasia [6].…”

“…In combination with a nutritionally balanced diet, exercise training is a remarkable potential strategy for lipolytic activity, preventing rapid ECM expansion and attenuating inflammatory conditions in parallel with insulin action improvements [7]. Some evidence showed that exercise training might play an essential role in adipose tissue ECM remodeling, previously altered by high-fat (HF) diets in rodents [7,16], promoting a decrease in the collagen deposition, metalloproteinase (MMP) activity, and gene expression of ECM components, which are essential for maintaining metabolic health. In contrast, the impact of controlled exercise on adipose tissue ECM in obese humans is scarce and controversial, probably due to the lack of precise control of dietary intake and demographic factors [17,18].…”

The Effects of Exercise on White and Brown Adipose Tissue Cellularity, Metabolic Activity and Remodeling

“…One study found that treadmill training in mice fed a HFD decreased fibrosis in VIS adipose tissue measured by decreased Picro Sirius red staining and decreased fibrotic gene expression ( Kawanishi et al, 2013b ). Additionally, another study investigating fibrosis in obese mice following exercise intervention found that exercise attenuated collagen deposition and fibrotic gene expression in VIS adipose tissue ( Li et al, 2021 ). In comparison, aerobic exercise in obese adults did not affect any markers of fibrosis in SUB adipose tissue ( Van Pelt et al, 2017 ).…”