A 12-week aerobic exercise intervention results in improved metabolic function and lower adipose tissue and ectopic fat in high-fat diet fed rats.

Venkatesh Gopalan,Rengaraj Anantharaj,Jorming Goh,Suresh Anand Sadananthan,Giang Thi Thu Le,Kavita Kaur,Jadegoud Yaligar,S Sendhil Velan,Sanjay Kumar Verma,Navin Michael

doi:10.1042/bsr20201707

Abstract

Investigations of long-term exercise interventions in humans to reverse obesity is expensive and is hampered by poor compliance and confounders. In the present study, we investigated intrahepatic and muscle fat, visceral and subcutaneous fat pads, plasma metabolic profile and skeletal muscle inflammatory markers in response to 12-week aerobic exercise in an obese rodent model. Six-week-old male Wistar rats (n=20) were randomized to chow-fed control (Control, n=5), sedentary high-fat diet (HFD, n=5), chow-fed exercise (Exercise, n=5) and HFD-fed exercise (HFD+Exercise, n=5) groups. The exercise groups were subjected to 12 weeks of motorized treadmill running at a speed of 18 m/min for 30 min/day. Differences in post-intervention measures were assessed by analysis of covariance (ANCOVA), adjusted for baseline bodyweight and pre-intervention measures, where available. Post-hoc analyses were performed with Bonferroni correction. Plasma metabolic profile was worsened and fat pads, ectopic fat in muscle and liver and inflammatory markers in skeletal muscle were elevated in sedentary HFD-fed animals relative to chow-fed controls. HFD+Exercise animals had significantly lower leptin (P=0.0004), triglycerides (P=0.007), homeostatic model assessment of insulin resistance (HOMA-IR; P=0.065), intramyocellular lipids (IMCLs; P=0.003), intrahepatic lipids (IHLs; P<0.0001), body fat% (P=0.001), subcutaneous adipose tissue (SAT; P<0.0001), visceral adipose (P<0.0001) and total fat mass (P<0.0001), relative to sedentary HFD-fed animals, despite only modestly lower bodyweight. Messenger RNA (mRNA) expression of inflammatory markers Interleukin 6 (IL6) and Tumor necrosis factor α (TNFα) were also reduced with aerobic exercise in skeletal muscle. Our results suggest that 12 weeks of aerobic exercise training is effective in improving metabolic health, fat depots, ectopic fat and inflammation even against a high-fat dietary background.

Highlights

Obesity and its associated comorbidities represent major challenges to human health in the 21st century [1]
Estimated marginal means after adjustment for baseline covariate using analysis of covariance (ANCOVA) are shown for bodyweight and biochemical measurements (Figure 2), ectopic fat (IMCL and intrahepatic lipid (IHL)) assessments (Figure 3), fat pads and adiposity assessments (Figure 4), and organ wet weights (Figure 5) of soleus muscle, tibialis muscle and liver
Within the high-fat diet (HFD) fed animal, exercise was found to result in significantly lower leptin (P=0.0004), triglycerides (P=0.007), Intramyocellular lipid (IMCL) (P=0.003), IHL (P

Summary

Introduction

Obesity and its associated comorbidities represent major challenges to human health in the 21st century [1]. While obesity represents a state of fat-excess, the metabolically deleterious effects of obesity may stem from increased fat accumulation in pathogenic depots, in the abdominal compartments [2] and ectopic sites like liver and muscle [3]. Accumulation of fat in hepatocytes (fatty liver disease) is associated with impaired hepatic glucose and fat metabolism leading to hepatic/systemic insulin resistance [5,6]. Intramyocellular lipid (IMCL) is formed from the accumulation of lipid droplets within muscle cells and is associated with altered insulin signaling pathways, insulin resistance and risk of type 2 diabetes mellitus [8,9]. IMCL accumulation is related to dysregulation of fatty acid metabolism due to obesity-related mitochondrial dysfunction [10,11]

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