Deficiency of clusterin exacerbates high-fat diet-induced insulin resistance in male mice

Min Jung Kwon, Tae Jin Ju, Jung Yoon Heo, Yong Woon Kim, Jong Yeon Kim, Kyu Chang Won, Jae Ryong Kim, Young Kyung Bae, In Sun Park, Bon Hong Min, In Kyu Lee, So Young Park

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Abstract

The present study examined the role of clusterin in insulin resistance in high fat-fed wild-type and clusterin knockout (KO) mice. The plasma levels of glucose and C-peptide and islet size were increased in clusterinKOmice after an 8-week high-fat diet. In an ip glucose tolerance test, the area under the curve for glucose was not different, whereas the area under the curve for insulin was higher in clusterin KO mice. In a hyperinsulinemic-euglycemic clamp, the clamp insulin levels were higher in clusterin KO mice after the high-fat diet. After adjusting for the clamp insulin levels, the glucose infusion rate, suppression of hepatic glucose production, and glucose uptake were lower in clusterin KO mice in the high fat-fed group. The plasma levels of clusterin and clusterin mRNA levels in the skeletal muscle and liver were increased by the high-fat diet. The mRNA levels of the antioxidant enzymes were lower, and the mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 1 and cytokines and protein carbonylation were higher in the skeletal muscle and liver in clusterin KO mice after the high-fat diet. Palmitate-induced gene expressions of NOX1 and cytokines were higher in the primary cultured hepatocytes of clusterin KO mice compared with the wild-type mice. Clusterin inhibited the gene expression and reactive oxygen species generation by palmitate in the hepatocytes and C2C12.AKTphosphorylation by insulin was reduced in the hepatocytes of clusterin KO mice. These results suggest that clusterin plays a protective role against high-fat diet-induced insulin resistance through the suppression of oxidative stress and inflammation.

Original languageEnglish
Pages (from-to)2089-2101
Number of pages13
JournalEndocrinology
Volume155
Issue number6
DOIs
Publication statusPublished - 2014 Jan 1

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Clusterin
High Fat Diet
Insulin Resistance
Knockout Mice
Glucose
Insulin
Hepatocytes
Palmitates
Messenger RNA
Area Under Curve
Liver
Skeletal Muscle
Fats
Protein Carbonylation
Cytokines
Gene Expression
Glucose Clamp Technique
C-Peptide
Glucose Tolerance Test
NADP

ASJC Scopus subject areas

  • Endocrinology

Cite this

Kwon, M. J., Ju, T. J., Heo, J. Y., Kim, Y. W., Kim, J. Y., Won, K. C., ... Park, S. Y. (2014). Deficiency of clusterin exacerbates high-fat diet-induced insulin resistance in male mice. Endocrinology, 155(6), 2089-2101. https://doi.org/10.1210/en.2013-1870

Deficiency of clusterin exacerbates high-fat diet-induced insulin resistance in male mice. / Kwon, Min Jung; Ju, Tae Jin; Heo, Jung Yoon; Kim, Yong Woon; Kim, Jong Yeon; Won, Kyu Chang; Kim, Jae Ryong; Bae, Young Kyung; Park, In Sun; Min, Bon Hong; Lee, In Kyu; Park, So Young.

In: Endocrinology, Vol. 155, No. 6, 01.01.2014, p. 2089-2101.

Research output: Contribution to journalArticle

Kwon, MJ, Ju, TJ, Heo, JY, Kim, YW, Kim, JY, Won, KC, Kim, JR, Bae, YK, Park, IS, Min, BH, Lee, IK & Park, SY 2014, 'Deficiency of clusterin exacerbates high-fat diet-induced insulin resistance in male mice', Endocrinology, vol. 155, no. 6, pp. 2089-2101. https://doi.org/10.1210/en.2013-1870
Kwon, Min Jung ; Ju, Tae Jin ; Heo, Jung Yoon ; Kim, Yong Woon ; Kim, Jong Yeon ; Won, Kyu Chang ; Kim, Jae Ryong ; Bae, Young Kyung ; Park, In Sun ; Min, Bon Hong ; Lee, In Kyu ; Park, So Young. / Deficiency of clusterin exacerbates high-fat diet-induced insulin resistance in male mice. In: Endocrinology. 2014 ; Vol. 155, No. 6. pp. 2089-2101.
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