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<p>Obesity has currently attained alarming proportions. Sedentary lifestyle and intake of high-calorie diet cause weight gain, increasing risks of hyperinsulinemia, hyperglycemia, and hyperlipidemia. The pathological state of insulin resistance paves way for type 2 diabetes, cardiovascular diseases and cancer. Chronic consumption of high-fat diet can cause male infertility though the mechanisms are not fully understood. Recent evidences in male reproduction establish impact of SIRT1 on several aspects including spermatogenesis and steroidogenesis. As a key metabolic regulator, SIRT1 influences stress responses, inflammation, apoptosis and mitochondrial oxidative metabolism. It is connected with hypothalamic-pituitary-gonadal axis and insulin signaling. Physical exercise can activate SIRT1 but data are inconsistent. Our aim was to evaluate regulation of SIRT1-mediated pathways specifically within testicular germ cells isolated from mice models of diet-induced obesity with and without exercise intervention. After acclimatization, adult male mice were randomly sorted into two groups fed with low-fat standard diet (SD) and high-fat diet (HFD). Subsets of SD and HFD mice were subjected to moderate-intensity exercise regimen. Obesity disturbed HPG axis and reduced germ cell SIRT1 level. Inhibition of SIRT1/FoxO1 signaling elicited intense oxidative stress and high apoptotic rate. AMPK/SIRT1/PGC-1α axis was suppressed affecting germ cell mitochondrial membrane integrity and bioenergetics. Spermatogenesis was impaired in the lipid-laden germ cells. Exercise-induced amelioration of germ cell dysfunction in HFD mice is mechanistically connected with activation of SIRT1 signaling. The study addressed critical interplay between obesity, male infertility and metabolic regulation. The findings assert benefits of SIRT1 activation by lifestyle modifications for management of obesity-associated male infertility.</p>

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Effects of Diet-Induced Obesity and Exercise Intervention on Testicular Germ Cell Health: Modulation of SIRT1/FoxO1 and SIRT1/PGC-1α Signaling Axes

  • 期刊论文

  • 发表日期：

    2026年4月29日

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  • Soumyadeep Basu,
  • Snehasis Das,
  • Sutapa Mukherjee

摘要

Obesity has currently attained alarming proportions. Sedentary lifestyle and intake of high-calorie diet cause weight gain, increasing risks of hyperinsulinemia, hyperglycemia, and hyperlipidemia. The pathological state of insulin resistance paves way for type 2 diabetes, cardiovascular diseases and cancer. Chronic consumption of high-fat diet can cause male infertility though the mechanisms are not fully understood. Recent evidences in male reproduction establish impact of SIRT1 on several aspects including spermatogenesis and steroidogenesis. As a key metabolic regulator, SIRT1 influences stress responses, inflammation, apoptosis and mitochondrial oxidative metabolism. It is connected with hypothalamic-pituitary-gonadal axis and insulin signaling. Physical exercise can activate SIRT1 but data are inconsistent. Our aim was to evaluate regulation of SIRT1-mediated pathways specifically within testicular germ cells isolated from mice models of diet-induced obesity with and without exercise intervention. After acclimatization, adult male mice were randomly sorted into two groups fed with low-fat standard diet (SD) and high-fat diet (HFD). Subsets of SD and HFD mice were subjected to moderate-intensity exercise regimen. Obesity disturbed HPG axis and reduced germ cell SIRT1 level. Inhibition of SIRT1/FoxO1 signaling elicited intense oxidative stress and high apoptotic rate. AMPK/SIRT1/PGC-1α axis was suppressed affecting germ cell mitochondrial membrane integrity and bioenergetics. Spermatogenesis was impaired in the lipid-laden germ cells. Exercise-induced amelioration of germ cell dysfunction in HFD mice is mechanistically connected with activation of SIRT1 signaling. The study addressed critical interplay between obesity, male infertility and metabolic regulation. The findings assert benefits of SIRT1 activation by lifestyle modifications for management of obesity-associated male infertility.