Enterostatin deficiency increases serum cholesterol but does not influence growth and food intake in mice.
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.
Miller
Rita
R
Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
D'Agostino
Dymphna
D
Erlanson-Albertsson
Charlotte
C
Lowe
Mark E
ME
D000818:Animals; D000831:Animals, Newborn; D016375:Antisense Elements (Genetics); D001831:Body Temperature / Q000502:physiology; D002784:Cholesterol / Q000097:blood*; D003089:Colipases / Q000172:deficiency* / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating / Q000235:genetics / Q000502:physiology*; D004792:Enzyme Precursors / Q000172:deficiency* / Q000235:genetics*; D006128:Growth / Q000502:physiology*; D006728:Hormones / Q000097:blood; D007408:Intestinal Absorption / Q000235:genetics; D008660:Metabolism / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015430:Weight Gain / Q000235:genetics
D016375:Antisense Elements (Genetics); D003089:Colipases; D004041:Dietary Fats; D004792:Enzyme Precursors; D006728:Hormones; C037107:procolipase; D004247:DNA; D002784:Cholesterol