Osteocalcin protects against nonalcoholic steatohepatitis in a mouse model of metabolic syndrome

Anisha A. Gupte, Omaima M. Sabek, Daniel Fraga, Laurie J. Minze, Satoru Nishimoto, Joey Z. Liu, Solmaz Afshar, Lillian Gaber, Christopher J. Lyon, A. Osama Gaber, Willa A. Hsueh

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4697-4705
Number of pages9
JournalEndocrinology
Volume155
Issue number12
DOIs
StatePublished - Dec 1 2014

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Osteocalcin
High Fat Diet
Insulin Resistance
Cholesterol
White Adipose Tissue
Non-alcoholic Fatty Liver Disease
Liver
Osteoblasts
Liver Diseases
Fibrosis
Insulin
Diet
Gene Expression
Bone and Bones
Therapeutics
Genes

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Gupte, A. A., Sabek, O. M., Fraga, D., Minze, L. J., Nishimoto, S., Liu, J. Z., ... Hsueh, W. A. (2014). Osteocalcin protects against nonalcoholic steatohepatitis in a mouse model of metabolic syndrome. Endocrinology, 155(12), 4697-4705. https://doi.org/10.1210/en.2014-1430

Osteocalcin protects against nonalcoholic steatohepatitis in a mouse model of metabolic syndrome. / Gupte, Anisha A.; Sabek, Omaima M.; Fraga, Daniel; Minze, Laurie J.; Nishimoto, Satoru; Liu, Joey Z.; Afshar, Solmaz; Gaber, Lillian; Lyon, Christopher J.; Gaber, A. Osama; Hsueh, Willa A.

In: Endocrinology, Vol. 155, No. 12, 01.12.2014, p. 4697-4705.

Research output: Contribution to journalArticle

Gupte, AA, Sabek, OM, Fraga, D, Minze, LJ, Nishimoto, S, Liu, JZ, Afshar, S, Gaber, L, Lyon, CJ, Gaber, AO & Hsueh, WA 2014, 'Osteocalcin protects against nonalcoholic steatohepatitis in a mouse model of metabolic syndrome', Endocrinology, vol. 155, no. 12, pp. 4697-4705. https://doi.org/10.1210/en.2014-1430
Gupte, Anisha A. ; Sabek, Omaima M. ; Fraga, Daniel ; Minze, Laurie J. ; Nishimoto, Satoru ; Liu, Joey Z. ; Afshar, Solmaz ; Gaber, Lillian ; Lyon, Christopher J. ; Gaber, A. Osama ; Hsueh, Willa A. / Osteocalcin protects against nonalcoholic steatohepatitis in a mouse model of metabolic syndrome. In: Endocrinology. 2014 ; Vol. 155, No. 12. pp. 4697-4705.
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