Abstract

This study evaluated the contributions of carboxyl ester lipase (CEL) and pancreatic triglyceride lipase (PTL) in lipid nutrient absorption. Results showed PTL deficiency has minimal effect on triacylglycerol (TAG) absorption under low fat dietary conditions. Interestingly, PTL(-)(/)(-) mice displayed significantly reduced TAG absorption compared with wild type mice under high fat/high cholesterol dietary conditions (80.1 +/- 3.7 versus 91.5 +/- 0.7%, p < 0.05). Net TAG absorption was reduced further to 61.1 +/- 3.8% in mice lacking both PTL and CEL. Cholesterol absorption was 41% lower in PTL(-/-) mice compared with control mice (p < 0.05), but this difference was not exaggerated in PTL(-/-), CEL(-/-) mice. Retinyl palmitate absorption was reduced by 45 and 60% in PTL(-/-) mice (p < 0.05) and PTL(-/-), CEL(-/-) mice (p < 0.01), respectively. After 15 weeks of feeding, the high fat/high cholesterol diet, wild type, and CEL(-/-) mice gained approximately 24 g of body weight. However, body weight gain was 6.2 and 8.6 g less (p < 0.01) in PTL(-/-) and PTL(-/-), CEL(-/-) mice, respectively, despite their consumption of comparable amounts of the high fat/high cholesterol diet. The decrease body weight gain in PTL(-/-) and PTL(-/-), CEL(-/-) mice was attributed to their absorption of fewer calories from the high fat/high cholesterol diet, thereby resulting in less fat mass accumulation than that observed in wild type and CEL(-/-) mice. Thus, this study documents that PTL and CEL serve complementary functions, working together to mediate the absorption of a major portion of dietary fat and fat-soluble vitamin esters. The reduced lipid absorption efficiency due to PTL and CEL inactivation also resulted in protection against diet-induced obesity.

Highlights

  • Molecular events involved in these processes remain poorly described

  • Triacylglycerol and Cholesterol Absorption in Mice—We have previously reported a reduced rate of TAG absorption in PTLϪ/Ϫ mice, but overall fat absorption efficiency was similar between PTLϩ/ϩ and PTLϪ/Ϫ mice when they were maintained on a low fat chow diet (1)

  • The current study examined TAG absorption in PTLϪ/Ϫ, CELϪ/Ϫ, and PTLϪ/Ϫ,CELϪ/Ϫ double knock-out mice when the animals were maintained under high fat/high cholesterol dietary conditions utilizing the nonabsorbable lipid-based tracer sucrose polybehenate as a marker of nonabsorbed lipid excreted in feces (8)

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Summary

Introduction

Molecular events involved in these processes remain poorly described Dietary lipids, such as triacylglycerol (TAG), phospholipids, cholesteryl esters, and retinyl esters must be cleaved by intestinal hydrolases before absorption. In vitro studies examining lipolytic activities in pancreatic extracts from PTLϪ/Ϫ and CELϪ/Ϫ mice provided insights to the identity of enzymes responsible for TAG and retinyl ester hydrolysis. Significant colipase-dependent retinyl ester hydrolytic activity was demonstrated in pancreatic extracts from both CELϩ/ϩ and CELϪ/Ϫ mice (7) This colipase dependence suggests that PTL may serve as a retinyl ester hydrolase in the digestive tract. In the current study we crossed PTLϪ/Ϫ mice with CELϪ/Ϫ mice to obtain mice lacking both enzymes to test the hypothesis that PTL and CEL serve a mutually compensatory role in assuring that sufficient lipolytic enzymes are available to catalyze absorption of dietary lipid nutrients. We took advantage of the availability of mice lacking one or both of these lipolytic enzymes in the digestive tract to assess their importance in dictating susceptibility to diet-induced obesity

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