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Loss of intestinal GATA4 prevents diet-induced obesity and promotes insulin sensitivity in mice. Am J Physiol Endocrinol Metab 2011 Mar;300(3):E478-88

Date

12/24/2010

Pubmed ID

21177287

Pubmed Central ID

PMC3163292

DOI

10.1152/ajpendo.00457.2010

Scopus ID

2-s2.0-79952144546   11 Citations

Abstract

Transcriptional regulation of small intestinal gene expression controls plasma total cholesterol (TC) and triglyceride (TG) levels, which are major determinants of metabolic diseases. GATA4, a zinc finger domain transcription factor, is critical for jejunal identity, and intestinal GATA4 deficiency leads to a jejunoileal transition. Although intestinal GATA4 ablation is known to misregulate jejunal gene expression, its pathophysiological impact on various components of metabolic syndrome remains unknown. Here, we used intestine-specific GATA4 knockout (GATA4iKO) mice to dissect the contribution of GATA4 on obesity development. We challenged adult GATA4iKO mice and control littermates with a Western-type diet (WTD) for 20 wk. Our findings show that WTD-fed GATA4iKO mice are resistant to diet-induced obesity. Accordingly, plasma TG and TC levels are markedly decreased. Intestinal lipid absorption in GATA4iKO mice was strongly reduced, whereas luminal lipolysis was unaffected. GATA4iKO mice displayed a greater glucagon-like peptide-1 (GLP-1) release on normal chow and even after long-term challenge with WTD remained glucose sensitive. In summary, our findings show that the absence of intestinal GATA4 has a beneficial effect on decreasing intestinal lipid absorption causing resistance to hyperlipidemia and obesity. In addition, we show that increased GLP-1 release in GATA4iKO mice decreases the risk for development of insulin resistance.

Author List

Patankar JV, Chandak PG, Obrowsky S, Pfeifer T, Diwoky C, Uellen A, Sattler W, Stollberger R, Hoefler G, Heinemann A, Battle M, Duncan S, Kratky D, Levak-Frank S

Author

Michele A. Battle PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adipose Tissue
Animals
Diet
Dietary Fats
Enzyme-Linked Immunosorbent Assay
Feces
GATA4 Transcription Factor
Gastric Emptying
Glucagon-Like Peptide 1
Glucose Tolerance Test
Hyperlipidemias
Insulin Resistance
Intestinal Absorption
Intestinal Mucosa
Lipolysis
Magnetic Resonance Imaging
Mice
Mice, Knockout
Obesity
RNA
Reverse Transcriptase Polymerase Chain Reaction
Tissue Distribution