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PMID: 11172066 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 4 ·2001-02-13 ·Pages 2005-10

Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF

Abstract

Adipocyte complement-related protein (30 kDa) (Acrp30), a secreted protein of unknown function, is exclusively expressed in differentiated adipocytes; its mRNA is decreased in obese humans and mice. Here we describe novel pharmacological properties of the protease-generated globular head domain of Acrp30 (gAcrp30). Acute treatment of mice with gAcrp30 significantly decreased the elevated levels of plasma free fatty acids caused either by administration of a high fat test meal or by i.v. injection of Intralipid. This effect of gAcrp30 was caused, at least in part, by an acute increase in fatty acid oxidation by muscle. As a result, daily administration of a very low dose of gAcrp30 to mice consuming a high-fat/sucrose diet caused profound and sustainable weight reduction without affecting food intake. Thus, gAcrp30 is a novel pharmacological compound that controls energy homeostasis and exerts its effect primarily at the peripheral level.

MeSH Terms
Adipocytes/metabolism Adiponectin Amino Acid Sequence Animals Blood Glucose Blood Proteins/metabolism Endopeptidases/metabolism Fatty Acids/metabolism Glucagon/metabolism Humans Insulin/metabolism Intercellular Signaling Peptides and Proteins Leptin/metabolism Male Mice Mice, Inbred C57BL Molecular Sequence Data Muscle, Skeletal/metabolism Oxidation-Reduction Protein Processing, Post-Translational Proteins Triglycerides/blood Weight Loss
Chemicals
Adiponectin Blood Glucose Blood Proteins Fatty Acids Insulin Intercellular Signaling Peptides and Proteins Leptin Proteins Triglycerides Glucagon Endopeptidases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fruebis J
Genset Corporation, Functional Genomics, 875 Prospect Street, No. 206, La Jolla, CA 92037, USA.
Tsao T S
Javorschi S
Ebbets-Reed D
Erickson M R
Yen F T
Bihain B E
Lodish H F
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.041591798
Published
2001-02-13
Epub
2001-00-06
Pages
2005-10
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC29372
Subset
IM
Grants
NIDDK NIH HHS · R37 DK047618 · United States
NIDDK NIH HHS · R37 DK47618 · United States
Databases
GENBANK
U37222
External Links
PubMed source DOI: 10.1073/pnas.041591798 PMC Full Text View journal details
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