Voluntary exercise improves hypothalamic and metabolic function in obese mice

Abstract

Exercise plays a critical role in regulating glucose homeostasis and body weight. However, the mechanism of exercise on metabolic functions associated with the CNS has not been fully understood. C57BL6 male mice (n = 45) were divided into three groups: normal chow diet, high-fat diet (HFD) treatment, and HFD along with voluntary running wheel exercise training for 12 weeks. Metabolic function was examined by the Comprehensive Lab Animal Monitoring System and magnetic resonance imaging; phenotypic analysis included measurements of body weight, food intake, glucose and insulin tolerance tests, as well as insulin and leptin sensitivity studies. By immunohistochemistry, the amount changes in the phosphorylation of signal transducer and activator of transcription 3, neuronal proliferative maker Ki67, apoptosis positive cells as well as pro-opiomelanocortin (POMC)-expressing neurons in the arcuate area of the hypothalamus was identified. We found that 12 weeks of voluntary exercise training partially reduced body weight gain and adiposity induced by an HFD. Insulin and leptin sensitivity were enhanced in the exercise training group verses the HFD group. Furthermore, the HFD-impaired POMC-expressing neuron is remarkably restored in the exercise training group. The restoration of POMC neuron number may be due to neuroprotective effects of exercise on POMC neurons, as evidenced by altered proliferation and apoptosis. In conclusion, our data suggest that voluntary exercise training improves metabolic symptoms induced by HFD, in part through protected POMC-expressing neuron from HFD and enhanced leptin signaling in the hypothalamus that regulates whole-body energy homeostasis. Exercise restores HFD-impaired POMC-expression neuronb t laing, k do and others

Diet‐induced DNA methylation within the hypothalamic arcuate nucleus and dysregulated leptin and insulin signaling in the pathophysiology of obesity

“…Exercise is a powerful antiobesity tool, with several studies indicating that exercise can have positive outcomes through affecting epigenetics (Brown, ; Nitert et al, ; Ronn et al, ). In a study using mice, it was reported that exercise had positive effects on restoring POMC action impaired by HFD (Laing et al, ). It would be interesting to investigate whether this effect was achieved through modulation of POMC DNA methylation patterns.…”

“…In a study using mice, it was reported that exercise had positive effects on restoring POMC action impaired by HFD (Laing et al, 2016). It would be interesting to investigate whether this effect was achieved through modulation of POMC DNA methylation patterns.…”

Beta-Aminoisobutyric Acid Inhibits Hypothalamic Inflammation by Reversing Microglia Activation

“…A growing body of evidence has demonstrated that exercise is an effective therapeutic intervention for treating obesity and the related secondary complications [10,11]. Intriguingly, voluntary exercise gives rise to anti-inflammatory effects against fat-rich diet-induced hypothalamic inflammation [10,12]. However, the endocrine substances that mediate the benefits of exercise are yet to be elucidated.…”

Acute physical exercise increases APPL1/PI3K signaling in the hypothalamus of lean mice

“…Knowing APPL1 activates PI3K protein (Cleasby et al., ), we hypothesize this mechanism may occur in the central nervous system (CNS), especially in the hypothalamus, an important structure responsible for the food intake control. As a non‐pharmacological strategy, physical exercise has positive effects on the control of hypothalamic disorders and food intake (Laing et al., ; Rodrigues et al., ; Ropelle et al., ).…”