Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents

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Munoz, V. R. ; Gaspar, R. C. ; Mancini, M. C. S. ; de Lima, R. D. ; Vieira, R. F. L. ; Crisol, B. M. ; Antunes, G. C. ; Trombeta, J. C. S. ; Bonfante, I. L. P. ; Simabuco, F. M. ; da Silva, A. S. R. ; Cavaglieri, C. R. ; Ropelle, E. R. ; Cintra, D. E. ; Pauli, J. R.

• Document type: Journal article
• Source: Journal of Endocrinological Investigation; v. N/A, p. 13-pg., 2022-11-01.

Abstract

Purpose Aging is associated with changes in glucose homeostasis related to both decreased insulin secretion and/or impaired insulin action, contributing to the high prevalence of type 2 diabetes (T2D) in the elderly population. Additionally, studies are showing that chronically high levels of circulating insulin can also lead to insulin resistance. In contrast, physical exercise has been a strategy used to improve insulin sensitivity and metabolic health. However, the molecular alterations resulting from the effects of physical exercise in the liver on age-related hyperinsulinemia conditions are not yet fully established. This study aimed to investigate the effects of 7 days of aerobic exercise on hepatic metabolism in aged hyperinsulinemic rats (i.e., Wistar and F344) and in Slc2a4(+/-) mice (hyperglycemic and hyperinsulinemic mice). Results Both aged models showed alterations in insulin and glucose tolerance, which were associated with essential changes in hepatic fat metabolism (lipogenesis, gluconeogenesis, and inflammation). In contrast, 7 days of physical exercise was efficient in improving whole-body glucose and insulin sensitivity, and hepatic metabolism. The Slc2a4(+/-) mice presented significant metabolic impairments (insulin resistance and hepatic fat accumulation) that were improved by short-term exercise training. In this scenario, high circulating insulin may be an important contributor to age-related insulin resistance and hepatic disarrangements in some specific conditions. Conclusion In conclusion, our data demonstrated that short-term aerobic exercise was able to control mechanisms related to hepatic fat accumulation and insulin sensitivity in aged rodents. These effects could contribute to late-life metabolic health and prevent the development/progression of age-related T2D. (AU)

• FAPESP's process: 16/18488-8 - The role of physical exercise on molecular pathways of glucose uptake in GLUT-4 knockout mice
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/11820-5 - Nr1d1 function on the aging-associated Sarcopenia
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/20872-6 - Effects of physical exercise on Rock protein signaling pathway, and lipogenic regulation and gluconeogenesis in the liver of aged rats
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/08692-5 - Analysis of the rev-erb-alpha protein interactome through immunoprecipitation of target protein and identification of possible ligands by mass spectrometry in cell culture
• Grantee: Vitor Rosetto Muñoz
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/13443-1 - Implications of aerobic exercise on the Notch 1 signaling pathway and regulation of lipogenesis and gluconeogenesis in the liver
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/26000-2 - The role of Rock protein on glucose uptake in the skeletal muscle of exercised rodents during the aging process
• Grantee: Vitor Rosetto Muñoz
• Support Opportunities: Scholarships in Brazil - Master