ArticleMolecular metabolism2019
Loss of FoxOs in muscle reveals sex-based differences in insulin sensitivity but mitigates diet-induced obesity.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Gut Microbiota-microRNA Interactions and Obesity Pathophysiology: A Systematic Review of Integrated Studies.International journal of molecular sciences · 2024Pooled it
- Loss of FoxO in skeletal muscle leads to disrupted muscle metabolism and exacerbates starvation-induced hepatic steatosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Aptamer-Conjugated Exosomes Ameliorate Diabetes-Induced Muscle Atrophy by Enhancing SIRT1/FoxO1/3a-Mediated Mitochondrial Function.Journal of cachexia, sarcopenia and muscle · 2025Article
- Temporal sex specific brain gene expression pattern during early rat embryonic development.Frontiers in cell and developmental biology · 2024Article
- Loss of FoxOs in muscle increases strength and mitochondrial function during aging.Journal of cachexia, sarcopenia and muscle · 2023Article
- Sex Differences in Glucose Homeostasis.Handbook of experimental pharmacology · 2023Article
- Phytochemicals targeting NAFLD through modulating the dual function of forkhead box O1 (FOXO1) transcription factor signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2022Review
- Functional resilience of C57BL/6J mouse heart to dietary fat overload.American journal of physiology. Heart and circulatory physiology · 2021Article
- Insulin and IGF-1 receptors regulate complex I-dependent mitochondrial bioenergetics and supercomplexes via FoxOs in muscle.The Journal of clinical investigation · 2021Article
- Multi-omic profiling of primary mouse neutrophils predicts a pattern of sex and age-related functional regulation.Nature aging · 2021Article
- Role of FoxO1 in regulating autophagy in type 2 diabetes mellitus (Review).Experimental and therapeutic medicine · 2021Review
- Molecular Insulin Actions Are Sexually Dimorphic in Lipid Metabolism.Frontiers in endocrinology · 2021Review
- Correlation between alterations of gut microbiota andAnnals of translational medicine · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveGender influences obesity-related complications, including diabetes. Females are more protected from insulin resistance after diet-induced obesity, which may be related to fat accumulation and muscle insulin sensitivity. FoxOs regulate muscle atrophy and are targets of insulin action, but their role in muscle insulin sensitivity and mitochondrial metabolism is unknown.
methodsWe measured muscle insulin signaling, mitochondrial energetics, and metabolic responses to a high-fat diet (HFD) in male and female muscle-specific FoxO1/3/4 triple knock-out (TKO) mice.
resultsIn male TKO muscle, insulin-stimulated AKT activation was decreased. AKT2 protein and mRNA levels were reduced and insulin receptor protein and IRS-2 mRNA decreased. These changes contributed to decreased insulin-stimulated glucose uptake in glycolytic muscle in males. In contrast, female TKOs maintain normal insulin-mediated AKT phosphorylation, normal AKT2 levels, and normal glucose uptake in glycolytic muscle. When challenged with a HFD, fat gain was attenuated in both male and female TKO mice, and associated with decreased glucose levels, improved glucose homeostasis, and reduced muscle triglyceride accumulation. Furthermore, female TKO mice showed increased energy expenditure, relative to controls, due to increased lean mass and maintenance of mitochondrial function in muscle.
conclusionsFoxO deletion in muscle uncovers sexually dimorphic regulation of AKT2, which impairs insulin signaling in male mice, but not females. However, loss of FoxOs in muscle from both males and females also leads to muscle hypertrophy and increases in metabolic rate. These factors mitigate fat gain and attenuate metabolic abnormalities in response to a HFD.
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