Deletion of Tis7 Protects Mice from High-Fat Diet-Induced Weight Gain and Blunts the Intestinal Adaptive Response Postresection
After loss of intestinal surface area, the remaining bowel undergoes a morphometric and functional adaptive response. Enterocytic expression of the transcriptional coregulator tetradecanoyl phorbol acetate induced sequence 7 (Tis7) is markedly increased in a murine model of intestinal adaptation. Mi...
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Veröffentlicht in: | The Journal of nutrition 2010-11, Vol.140 (11), p.1907-1914 |
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Sprache: | eng |
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Zusammenfassung: | After loss of intestinal surface area, the remaining bowel undergoes a morphometric and functional adaptive response. Enterocytic expression of the transcriptional coregulator tetradecanoyl phorbol acetate induced sequence 7 (Tis7) is markedly increased in a murine model of intestinal adaptation. Mice overexpressing Tis7 in intestine have greater triglyceride absorption and weight gain when fed a high-fat diet (42% energy) than their wild-type (WT) littermates fed the same diet. These and other data suggest that Tis7 has a unique role in nutrient absorptive and metabolic adaptation. Herein, male Tis7⁻/⁻ and WT mice were fed a high-fat diet (42% energy) for 8 wk. Weight was monitored and metabolic analyses and hepatic and intestinal lipid concentrations were compared after 8 wk. Intestinal lipid absorption and metabolism studies and intestinal resection surgeries were performed in separate groups of Tis7⁻/⁻ and WT mice. At 8 wk, weight gain was less and jejunal mucosal and hepatic triglyceride and cholesterol concentrations were lower in Tis7⁻/⁻ mice than in the WT controls. Following corn oil gavage, serum cholesterol, triglyceride, and FFA concentrations were lower in the Tis7⁻/⁻ mice than in the WT mice. Incorporation of oral ³[H] triolein into intestinal mucosal cholesterol ester and FFA was less in Tis7⁻/⁻ compared with WT mice. Following resection, crypt cell proliferation rates and villus heights were lower in Tis7⁻/⁻ than in WT mice, indicating a blunted adaptive response. Our results suggest a novel physiologic function for Tis7 in the gut as a global regulator of lipid absorption and metabolism and epithelial cell proliferation. |
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ISSN: | 0022-3166 1541-6100 |
DOI: | 10.3945/jn.110.127084 |