Enterostatin and its target mechanisms during regulation of fat intake.
A high-fat diet easily promotes hyperphagia giving an impression of an uncontrolled process. Fat digestion itself however provides control of fat intake through the digestion itself, carried out by pancreatic lipase and its protein cofactor colipase, and through enterostatin, a peptide released from procolipase during fat digestion. Procolipase (-/-) knockout mice have a severely reduced fat digestion and fat uptake, pointing to a major role of the digestive process itself. With a normal fat digestion, enterostatin basically restricts fat intake by preventing the overconsumption of fat. The mechanism for enterostatin might be an inhibition of a mu-opioid-mediated pathway, demonstrated through binding studies on SK-N-MC-cells and crude brain membranes. Another target protein of enterostatin is the beta-subunit of F1F0-ATPase, displaying a distinct binding of enterostatin, established through an aqueous two-phase partition system. The binding of enterostatin to F1-ATPase was partially displaced by beta-casomorphin, a peptide stimulating fat intake and acting competitively to enterostatin. We frame a hypothesis that regulation of fat intake through enterostatin contains a reward component, which is an F1-ATPase-mediated pathway, possibly complemented with an opioidergic pathway.
Berger
Karin
K
Department of Cell and Molecular Biology, Biomedical Center BMC, C11, Lund University, SE-221 84 Lund, Sweden.
Winzell
Maria Sörhede
MS
Mei
Jie
J
Erlanson-Albertsson
Charlotte
C
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D003089:Colipases / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004723:Endorphins / Q000494:pharmacology; D004792:Enzyme Precursors; D005223:Fats / Q000008:administration & dosage; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D008954:Models, Biological; D009434:Neural Pathways / Q000502:physiology; D011498:Protein Precursors / Q000502:physiology*; D000071256:Uncoupling Protein 1
D000701:Analgesics, Opioid; D002352:Carrier Proteins; D003089:Colipases; D004723:Endorphins; D004792:Enzyme Precursors; D005223:Fats; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011498:Protein Precursors; D000071256:Uncoupling Protein 1; C037107:procolipase; C021968:beta-casomorphins; C474451:F1F0-ATP synthase; D025261:Mitochondrial Proton-Translocating ATPases