Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 493, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2019.110480
Keywords
MicroRNA; Adiponectin; Obesity; Insulin resistance; Pioglitazone; NAFLD
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [15/24789-8, 15/24650-0]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [15/24789-8] Funding Source: FAPESP
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Pioglitazone has been used for the treatment of nonalcoholic fatty liver disease (NAFLD) related to diabetes. The role of adiponectin in pioglitazone-induced improvements in NAFLD was studied by using wild-type (adipoWT) and adiponectin knockout (adipoKO) mice. High-fat diet fed mice were insulin resistant, glucose intolerant and had increased hepatic lipid accumulation as evidenced by increased NAFLD activity score. Despite pioglitazone has improved insulin resistance in both genotypes, hepatic steatosis was only improved in adipoWT obese mice. Amelioration of NAFLD in adipoWT mice promoted by pioglitazone was associated with up-regulation of Pparg, Fgf21 and down-regulation of Pepck liver expression. On the other hand, resistance to pioglitazone treatment in adipoKO mice was associated with increased expression of miR-192 and Hsl, which was not followed by increased fatty acid oxidation. In conclusion, our data provides evidence that increased adiponectin production by pioglitazone is necessary for its beneficial action on NAFLD.
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