Exercise-induced lowering of fetuin-A may increase hepatic insulin sensitivity
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INTRODUCTION: Fetuin-A is a novel hepatokine, and there is preliminary evidence that it may contribute to the pathogenesis of type 2 diabetes. Exercise reduces fetuin-A, but the specific metabolic effects particularly as they relate to the regulation of insulin resistance are unknown. This led us to examine the effect of exercise training on circulating fetuin-A in relation to skeletal muscle and/or hepatic insulin resistance in obese adults. METHODS: Twenty older adults (66.3 ± 0.9 yr; body mass index, 34.1 ± 1.2 kg · m(-1)) participated in this prospective 12-wk study and underwent supervised exercise training (5 d · wk(-1), 60 min · d(-1) at approximately 85% HRmax). Insulin resistance was assessed using the euglycemic-hyperinsulinemic clamp (40 mU · m(-2) · min(-1)) with isotope dilution ([6,6-H2]-glucose). Skeletal muscle insulin sensitivity (rate of glucose disposal), hepatic insulin resistance (rate of glucose appearance × fasting insulin), metabolic flexibility (respiratory quotient clamp - respiratory quotient fasting), fetuin-A, high-molecular weight adiponectin, high-sensitivity C-reactive protein, leptin, and body fat (dual energy x-ray absorptiometry) were measured before and after the intervention. RESULTS: Exercise reduced body fat, high-sensitivity C-reactive protein, leptin and hepatic as well as skeletal muscle insulin resistance (each, P < 0.05). Fetuin-A was decreased by approximately 8% (pre, 1.01 ± 0.08, vs post, 0.89 ± 0.06 g · L(-1); P < 0.05) after the intervention, and lower fetuin-A after exercise correlated with lower hepatic insulin resistance (r = -0.46, P < 0.01), increased metabolic flexibility (r = -0.70, P < 0.01) and high-molecular weight adiponectin (r = -0.57, P < 0.01). CONCLUSIONS: Fetuin-A may contribute to exercise training-induced improvements in hepatic insulin resistance, CHO utilization, and inflammation in older obese adults. Further work is required to determine the cellular mechanism(s) of action for fetuin-A because this hepatokine is related to type 2 diabetes risk.
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A 12-week aerobic exercise training intervention decreased fetuin A levels in obese, insulin-resistant subjects, leading to decreased hepatic insulin resistance, total body fat, and fasting insulin levels.
“Another 12-week aerobic exercise training intervention, consisting of treadmill walking at 85% maximum heart rate for 60 min per session, decreased fetuin A levels in obese, insulin-resistant subjects, leading to decreased hepatic insulin resistance, total body fat, and fasting insulin levels [139].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [139]
The Methods (Subjects) describe 12 weeks of supervised exercise, mainly treadmill walking for 60 minutes at 85% maximum heart rate. The Abstract (Results) reports reductions in fetuin-A, body fat, and hepatic insulin resistance. However, the retrieved Results do not report a decrease in fasting insulin, and the paper describes fetuin-A’s relationship to hepatic insulin resistance as an association rather than establishing that its reduction caused the other changes. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAcute exercise in humans does not alter plasma fetuin-A, but chronic exercise might decrease it.
“Although acute exercise in humans does not alter plasma levels of fetuin-A97, chronic exercise might decrease plasma levels of fetuin-A72,101.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [101]
Chronic exercise in humans reduces circulating fetulin-A.
“Chronic exercise in humans also reduces circulating levels of fetulin-A72,101.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [101]
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- Authors
- Malin, S. K., del Rincon, J. P., Huang, H., & Kirwan, J. P.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Kirwan, John P.
- Venue
- Medicine & Science in Sports & Exercise
- Published
- 2014-11
- Volume
- 46
- Issue
- 11
- Pages
- 2085-2090
- ISSN
- 0195-9131 (ISSN-L)
- PMC
- PMC4640446
- OpenAlex
- W2090122979
- Cited by
- 85
- References
- 27
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 14 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 11 · 2019: 6 · 2018: 5 · 2017: 9 · 2016: 4 · 2015: 6 · 2014: 2
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Medicine & Science in Sports & Exercise (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG012834, R01AG12834)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089547-S1, T32DK007319, R01DK089547)
- National Center for Research Resources (UL1RR024989)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Keywords
- fetuin-A, exercise training, hepatic insulin resistance, skeletal muscle insulin sensitivity, hepatokines, type 2 diabetes, obesity, metabolic flexibility, high molecular weight adiponectin, inflammation, C-reactive protein, leptin, older adults, glucose metabolism, fat loss, hyperinsulinemic-euglycemic clamp, isotope dilution
- MeSH terms
- Aged, C-Reactive Protein, Female, Humans, Insulin Resistance, Liver, Male, Obesity, Exercise, Muscle, Skeletal, Leptin, Body Fat Distribution, Adiponectin, alpha-2-HS-Glycoprotein
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