Osteocalcin protects against nonalcoholic steatohepatitis in a mouse model of metabolic syndrome
Open accessAbstract
Nonalcoholic fatty liver disease, particularly its more aggressive form, nonalcoholic steatohepatitis (NASH), is associated with hepatic insulin resistance. Osteocalcin, a protein secreted by osteoblast cells in bone, has recently emerged as an important metabolic regulator with insulin-sensitizing properties. In humans, osteocalcin levels are inversely associated with liver disease. We thus hypothesized that osteocalcin may attenuate NASH and examined the effects of osteocalcin treatment in middle-aged (12-mo-old) male Ldlr(-/-) mice, which were fed a Western-style high-fat, high-cholesterol diet for 12 weeks to induce metabolic syndrome and NASH. Mice were treated with osteocalcin (4.5 ng/h) or vehicle for the diet duration. Osteocalcin treatment not only protected against Western-style high-fat, high-cholesterol diet-induced insulin resistance but substantially reduced multiple NASH components, including steatosis, ballooning degeneration, and fibrosis, with an overall reduction in nonalcoholic fatty liver disease activity scores. Further, osteocalcin robustly reduced expression of proinflammatory and profibrotic genes (Cd68, Mcp1, Spp1, and Col1a2) in liver and suppressed inflammatory gene expression in white adipose tissue. In conclusion, these results suggest osteocalcin inhibits NASH development by targeting inflammatory and fibrotic processes.
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OCN and irisin may exert direct anti-oxidant and anti-inflammatory effects in the liver.
“OCN [28,215] and irisin [61,65], on the other hand, may also exert direct anti-oxidant and anti-inflammatory effects in the liver.”
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 [215]
The Results report that osteocalcin reduced inflammatory-gene expression in mouse livers, and the Discussion says it may act directly on hepatic proinflammatory genes (page unavailable). The Discussion links reduced liver oxidative stress to improved glucose metabolism, not to a direct antioxidant effect of osteocalcin. Irisin is attributed to other citations in the citing sentence and is not assessed here. (LLM, conf=0.88)
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Self-citation
- Authors
- Gupte, A. A., Sabek, O. M., Fraga, D., Minze, L. J., Nishimoto, S. K., Liu, J. Z., Afshar, S., Gaber, L., Lyon, C. J., Gaber, A. O., & Hsueh, W. A.
- Affiliations
- Houston Methodist (US)
- University of Tennessee Health Science Center (US)
- Houston Methodist Research Institute (US)
- The Ohio State University (US)
- Corresponding author
- Hsueh, Willa A.
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2014-12-01
- Volume
- 155
- Issue
- 12
- Pages
- 4697-4705
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC5393336
- OpenAlex
- W2018063947
- Cited by
- 70
- References
- 40
- Citations by year
- 2026: 2 · 2024: 8 · 2023: 5 · 2022: 9 · 2021: 7 · 2020: 11 · 2019: 9 · 2018: 2 · 2017: 6 · 2016: 7 · 2015: 4
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U2CDK059630, U24DK059630)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- osteocalcin, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, metabolic syndrome, hepatic insulin resistance, Ldlr knockout mice, high-fat high-cholesterol diet, liver fibrosis, liver inflammation, adipose tissue inflammation, steatosis, ballooning degeneration, pro-inflammatory genes
- MeSH terms
- Animals, Disease Models, Animal, Drug Evaluation, Preclinical, Fatty Liver, Fibrosis, Inflammation, Insulin Resistance, Liver, Male, Osteocalcin, Metabolic Syndrome, Mice
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