Metformin treatment of juvenile mice alters aging-related developmental and metabolic phenotypes in sex-dependent and sex-independent manners.

Autor: Zhu Y; Department of Internal Medicine, Southern Illinois University School of Medicine, 801 N. Rutledge, P.O. Box 19628, Springfield, IL, 62702, USA., Engmann M; Department of Internal Medicine, Southern Illinois University School of Medicine, 801 N. Rutledge, P.O. Box 19628, Springfield, IL, 62702, USA., Medina D; Department of Internal Medicine, Southern Illinois University School of Medicine, 801 N. Rutledge, P.O. Box 19628, Springfield, IL, 62702, USA., Han X; Department of Internal Medicine, Southern Illinois University School of Medicine, 801 N. Rutledge, P.O. Box 19628, Springfield, IL, 62702, USA., Das P; Department of Physiology, Southern Illinois University SIU School of Medicine, 1135 Lincoln Drive, Life Science III, Room 2062, Carbondale, IL, 62901, USA., Bartke A; Department of Internal Medicine, Southern Illinois University School of Medicine, 801 N. Rutledge, P.O. Box 19628, Springfield, IL, 62702, USA., Ellsworth BS; Department of Physiology, Southern Illinois University SIU School of Medicine, 1135 Lincoln Drive, Life Science III, Room 2062, Carbondale, IL, 62901, USA., Yuan R; Department of Internal Medicine, Southern Illinois University School of Medicine, 801 N. Rutledge, P.O. Box 19628, Springfield, IL, 62702, USA. ryuan@siumed.edu.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2024 Jun; Vol. 46 (3), pp. 3197-3218. Date of Electronic Publication: 2024 Jan 16.
DOI: 10.1007/s11357-024-01067-6
Abstrakt: Metformin has attracted increasing interest for its potential benefits in extending healthspan and longevity. This study examined the effects of early-life metformin treatment on the development and metabolism of C57BL/6 J (B6) mice, with metformin administered to juvenile mice from 15 to 56 days of age. Metformin treatment led to decreased body weight in both sexes (P < 0.05, t-test). At 9 weeks of age, mice were euthanized and organ weights were recorded. The relative weight of retroperitoneal fat was decreased in females, while relative weights of perigonadal and retroperitoneal fat were decreased, and relative liver weight was increased in males (P < 0.05, t-test). Glucose and insulin tolerance tests (GTT and ITT) were conducted at the age of 7 weeks. ANOVA revealed a significant impairment in insulin sensitivity by the treatment, and a significantly interactive effect on glucose tolerance between sex and treatment, underscoring a disparity in GTT between sexes in response to the treatment. Metformin treatment reduced circulating insulin levels in fasting and non-fasting conditions for male mice, with no significant alterations observed in female mice. qRT-PCR analysis of glucose metabolism-related genes (Akt2, Glut2, Glut4, Irs1, Nrip1, Pi3k, Pi3kca, Pkca) in the liver and skeletal muscle reveals metformin-induced sex- and organ-specific effects on gene expression. Comparison with previous studies in heterogeneous UM-HET3 mice receiving the same treatment suggests that genetic differences may contribute to variability in the effects of metformin treatment on development and metabolism. These findings indicate that early-life metformin treatment affects development and metabolism in both sex- and genetics-dependent manners.
(© 2024. The Author(s), under exclusive licence to American Aging Association.)
Databáze: MEDLINE
Externí odkaz: