Diet Modifies Pioglitazone’s Influence on Hepatic PPARγ-Regulated Mitochondrial Gene Expression

المؤلفون المشاركون

Kulkarni, Sakil
Huang, Jiansheng
Tycksen, Eric
Cliften, Paul F.
Rudnick, David A.

المصدر

PPAR Research

العدد

المجلد 2020، العدد 2020 (31 ديسمبر/كانون الأول 2020)، ص ص. 1-20، 20ص.

الناشر

Hindawi Publishing Corporation

تاريخ النشر

2020-09-10

دولة النشر

مصر

عدد الصفحات

20

التخصصات الرئيسية

الأحياء

الملخص EN

Pioglitazone (Pio) is a thiazolidinedione (TZD) insulin-sensitizing drug whose effects result predominantly from its modulation of the transcriptional activity of peroxisome proliferator-activated-receptor-gamma (PPARγ).

Pio is used to treat human insulin-resistant diabetes and also frequently considered for treatment of nonalcoholic steatohepatitis (NASH).

In both settings, Pio’s beneficial effects are believed to result primarily from its actions on adipose PPARγ activity, which improves insulin sensitivity and reduces the delivery of fatty acids to the liver.

Nevertheless, a recent clinical trial showed variable efficacy of Pio in human NASH.

Hepatocytes also express PPARγ, and such expression increases with insulin resistance and in nonalcoholic fatty liver disease (NAFLD).

Furthermore, mice that overexpress hepatocellular PPARγ and Pio-treated mice with extrahepatic PPARγ gene disruption develop features of NAFLD.

Thus, Pio’s direct impact on hepatocellular gene expression might also be a determinant of this drug’s ultimate influence on insulin resistance and NAFLD.

Previous studies have characterized Pio’s PPARγ-dependent effects on hepatic expression of specific adipogenic, lipogenic, and other metabolic genes.

However, such transcriptional regulation has not been comprehensively assessed.

The studies reported here address that consideration by genome-wide comparisons of Pio’s hepatic transcriptional effects in wildtype (WT) and liver-specific PPARγ-knockout (KO) mice given either control or high-fat (HFD) diets.

The results identify a large set of hepatic genes for which Pio’s liver PPARγ-dependent transcriptional effects are concordant with its effects on RXR-DNA binding in WT mice.

These data also show that HFD modifies Pio’s influence on a subset of such transcriptional regulation.

Finally, our findings reveal a broader influence of Pio on PPARγ-dependent hepatic expression of nuclear genes encoding mitochondrial proteins than previously recognized.

Taken together, these studies provide new insights about the tissue-specific mechanisms by which Pio affects hepatic gene expression and the broad scope of this drug’s influence on such regulation.

نمط استشهاد جمعية علماء النفس الأمريكية (APA)

Kulkarni, Sakil& Huang, Jiansheng& Tycksen, Eric& Cliften, Paul F.& Rudnick, David A.. 2020. Diet Modifies Pioglitazone’s Influence on Hepatic PPARγ-Regulated Mitochondrial Gene Expression. PPAR Research،Vol. 2020, no. 2020, pp.1-20.
https://search.emarefa.net/detail/BIM-1206607

نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)

Kulkarni, Sakil…[et al.]. Diet Modifies Pioglitazone’s Influence on Hepatic PPARγ-Regulated Mitochondrial Gene Expression. PPAR Research No. 2020 (2020), pp.1-20.
https://search.emarefa.net/detail/BIM-1206607

نمط استشهاد الجمعية الطبية الأمريكية (AMA)

Kulkarni, Sakil& Huang, Jiansheng& Tycksen, Eric& Cliften, Paul F.& Rudnick, David A.. Diet Modifies Pioglitazone’s Influence on Hepatic PPARγ-Regulated Mitochondrial Gene Expression. PPAR Research. 2020. Vol. 2020, no. 2020, pp.1-20.
https://search.emarefa.net/detail/BIM-1206607

نوع البيانات

مقالات

لغة النص

الإنجليزية

الملاحظات

Includes bibliographical references

رقم السجل

BIM-1206607