Enterostatin deficiency increases serum cholesterol but does not influence growth and food intake in mice

Abstract

A pentapeptide released from procolipase, enterostatin, selectively attenuates dietary fat intake when administered peripherally or centrally. Enterostatin may act through the afferent vagus nerve and in the hypothalamus and amygdala, primarily in the central nucleus of the amygdala. To investigate the physiological role of endogenous enterostatin, we created an enterostatin-deficient, colipase-sufficient (Ent(-/-)) mouse. Ent(-/-) mice are viable, normally active, and fertile. They exhibit normal growth on low-fat and high-fat diets. Furthermore, Ent(-/-) mice develop diet-induced obesity, as do Ent(+/+) mice, and have normal responses to a two-macronutrient choice diet and to a switch from a high-fat to a low-fat diet. Levels of total serum (P = 0.004) and non-HDL (P <or= 0.001) cholesterol were higher and levels of HDL cholesterol (P = 0.01) were lower in Ent(-/-) than in wild-type mice. To determine whether enterostatin contributed to the decreased survival or whether colipase deficiency was the sole contributor, we administered enterostatin to procolipase-deficient (Clps(-/-)) mouse pups. Enterostatin significantly improved survival (P <or= 0.001). Our results demonstrate that enterostatin is not critically required to regulate food intake or growth, suggesting that other pathways may compensate for the loss of enterostatin. Enterostatin has developmental effects on survival of newborns and alters cholesterol metabolism.

Kinetic properties of mouse pancreatic lipase-related protein-2 suggest the mouse may not model human fat digestion

“…Under these conditions, TAG hydrolysis by either mPTL or mPLRP2 alone was nearly as effi cient as when both lipases were included in the assay. These results provide an explanation for the absence of signifi cant effects on dietary fat digestion in adult mice defi cient in either mPLRP2 or mPTL ( 6,30 ). Under physiological conditions, mPTL and mPLRP2 compete for the limited colipase to boost their lipase activity.…”

The mechanism exploration of the non‐colonic toxicity and obesity inhibition of food‐grade κ‐carrageenan by transcriptome

“…The expression reduction of Lep and Orm1 in H5% mice implied the remission of obesity and metabolic syndrome (Lee et al, 2010). Furthermore, it was possible that 5% carrageenan promoted lipid hydrolysis but inhibited lipid synthesis as evident by elevated enzymes expression of Scd1 and lowered Clps (Alberto and Luciano, 2012;Macdonald et al, 2008;Miller et al, 2009).…”

Enterostatin

“…19 This reduction in cholesterol levels occurs independent of the food suppressive effect of enterostatin and is dependent on cholecystokinin action. 29 The mechanism may be a stimulation of bile salt excretion into the feces by enterostatin, and after this, a conversion of cholesterol to bile salt resulting in reduced serum cholesterol levels takes place.…”

“…The enterostatin-deficient mouse (Ent −/−) displays a normal fat intake but has higher LDL + VLDL blood cholesterol levels and lower HDL cholesterol levels. 19 membrane seems to be a possible mechanism for enterostatin to affect various cellular processes.…”

“…2). 19 Enterostatin is released from pancreatic procolipase during digestion of fat and was first described as a peptide that promotes satiety for fat (Fig. 1).…”