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Peroxisome proliferator-activated receptor-α modulates insulin gene transcription factors and inflammation in adipose tissues in mice

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Abstract

We have recently reported that PPARα deficiency leads to hypoglycaemia and hypoinsulinemia in mice (Yessoufou et al. Endocrinology 147:4410–4418, 2006). Besides, these mice exhibited high adiposity with an inflammatory state. We, therefore, assessed, in this study, the effects of PPARα deficiency on the expression of mRNA encoding for the insulin gene transcription factors in pancreatic β-cells along with those implicated in inflammation in adipose tissues. On fasting, the adult PPARα-null mice were hypoglycemic. Serum insulin concentrations and its pancreatic mRNA transcripts were downregulated in PPARα-null mice, suggesting that PPARα gene deletion contributes to low insulin gene transcription. The PPARα gene deletion downregulates the mRNA expression of insulin gene transcription factors, i.e., Pdx-1, Nkx6.1, and MafA. Besides, the pancreatic function was diminished by PPARα deficiency as PPARα-null mice expressed low pancreatic Glut2 and glucokinase mRNA. PPARα-null mice also expressed high adiponectin and leptin mRNA levels compared to wild type animals. Adipose tissues of PPARα-null mice exhibited upregulation of CD14 and CD68 mRNA, generally expressed by macrophages. PPARα gene deletion downregulates the adipocyte mRNA of certain pro-inflammatory agents, like MCP-1, TNF-α, IL-1β, IL-6, and RANTES, though pro-inflammatory TLR-2 and TLR-4 mRNAs were upregulated in the adipose tissues. Our results suggest that PPARα deficiency, in mice, is implicated in the modulation of insulin gene transcription and inflammatory status in adipose tissues.

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Abbreviations

GK:

Glucokinase

Nkx6.1:

NK6 transcription factor related-locus-1

Pdx-1:

Pancreatic and duodenal homeobox-1

PPARα:

Peroxisome proliferator-activated receptor-α

MCP-1:

Monocyte-chemoattractant protein-1

RANTES:

Regulated on activation of normal T cell expressed and secreted

SREBP1c:

Sterol response element-binding protein 1c

TG:

Triglyceride

TLR:

Toll-like receptor

FFA:

Free fatty acids

WAT:

White adipose tissue

PBS:

Phosphate buffered saline

WT:

Wild type

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Acknowledgments

We thank Ministry of High Education, Republic of Benin, which granted a scholarship to Jean-Marc Atègbo and Eugène Attakpa. We express our sincere thanks to Dr. F. J. Gonzalez, National Cancer Institute who allowed us to use PPARα-null mice under the MTA number 1-23651-07.

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Authors and Affiliations

  1. Laboratory of Cell Biology and Physiology, Department of Biochemistry and Cellular Biology, Faculty of Sciences and Techniques, Institute of Biomedical and Applied Sciences (ISBA-Cotonou), University of Abomey-Calavi, Cotonou, Benin

    Akadiri Yessoufou & Kabirou Moutairou

  2. UPRES EA 4183 Lipids and Cell Signalling, Faculty of Life Sciences, University of Burgundy, 6 Boulevard Gabriel, 21000, Dijon, France

    Akadiri Yessoufou, Jean-Marc Atègbo, Eugène Attakpa, Aziz Hichami & Naim A. Khan

  3. Department of Animal Physiology, Faculty of Sciences and Techniques, University of Abomey-Calavi, Cotonou, Benin

    Jean-Marc Atègbo, Eugène Attakpa & Karim L. Dramane

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  1. Akadiri Yessoufou
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  2. Jean-Marc Atègbo
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  3. Eugène Attakpa
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  4. Aziz Hichami
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  5. Kabirou Moutairou
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  6. Karim L. Dramane
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  7. Naim A. Khan
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Correspondence to Naim A. Khan.

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A. Yessoufou and J.-M. Atègbo contributed equally to this work.

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Yessoufou, A., Atègbo, JM., Attakpa, E. et al. Peroxisome proliferator-activated receptor-α modulates insulin gene transcription factors and inflammation in adipose tissues in mice. Mol Cell Biochem 323, 101–111 (2009). https://doi.org/10.1007/s11010-008-9968-1

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