Body composition in geneknockouts of sulfur amino acid-metabolizing enzymes

Body composition in geneknockouts of sulfur amino acid-metabolizing enzymes Plasma concentrations of several amino acids are elevated in human obesity and insulin resistance, but there is no conclusive evidence on whether the amino acid alterations are causal. Dietary restriction of the essential SAA methionine (MR) in rats produces a hypermetabolic phenotype, with an integrated set of transcriptional changes in lipid enzymes in liver and adipose tissue. MR also induces an array of changes in methionine metabolites, including elevated plasma homocysteine and decreased cystathionine, cysteine, glutathione, and taurine. Several knockouts of enzymes acting downstream of methionine recapitulate the phenotypic results of MR, suggesting that the MR phenotype may be driven by changes distal to methionine. Here we review the changes in SAA and body composition in seven relevant knockout mouse models. All seven models feature decreased body weight, which in five of these have been further explored and shown to result from predominantly decreased fat mass. Common to several models is increased energy expenditure, enhanced insulin sensitivity, and protection against dietary obesity, as occurs in MR. A decrease in plasma total cysteine concentrations is also seen in most models. The lean phenotype could often be reversed by dietary supplementation of cysteine or choline, but not taurine, betaine or a H2S donor. Importantly, the plasma concentrations of both cysteine and choline are positively associated with fat mass in large populations studies, while taurine, betaine, and H2S are not. Collectively, the emerging data from dietary and knockout models are in harmony with human epidemiologic data, suggesting that the availability of key nutrients in the SAA pathway regulates fat storage pathways. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Body composition in geneknockouts of sulfur amino acid-metabolizing enzymes

Loading next page...
 
/lp/springer_journal/body-composition-in-geneknockouts-of-sulfur-amino-acid-metabolizing-TUjDyWru5G
Publisher
Springer US
Copyright
Copyright © 2014 by Springer Science+Business Media New York
Subject
Life Sciences; Cell Biology; Anatomy; Zoology
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-014-9527-x
Publisher site
See Article on Publisher Site

Abstract

Plasma concentrations of several amino acids are elevated in human obesity and insulin resistance, but there is no conclusive evidence on whether the amino acid alterations are causal. Dietary restriction of the essential SAA methionine (MR) in rats produces a hypermetabolic phenotype, with an integrated set of transcriptional changes in lipid enzymes in liver and adipose tissue. MR also induces an array of changes in methionine metabolites, including elevated plasma homocysteine and decreased cystathionine, cysteine, glutathione, and taurine. Several knockouts of enzymes acting downstream of methionine recapitulate the phenotypic results of MR, suggesting that the MR phenotype may be driven by changes distal to methionine. Here we review the changes in SAA and body composition in seven relevant knockout mouse models. All seven models feature decreased body weight, which in five of these have been further explored and shown to result from predominantly decreased fat mass. Common to several models is increased energy expenditure, enhanced insulin sensitivity, and protection against dietary obesity, as occurs in MR. A decrease in plasma total cysteine concentrations is also seen in most models. The lean phenotype could often be reversed by dietary supplementation of cysteine or choline, but not taurine, betaine or a H2S donor. Importantly, the plasma concentrations of both cysteine and choline are positively associated with fat mass in large populations studies, while taurine, betaine, and H2S are not. Collectively, the emerging data from dietary and knockout models are in harmony with human epidemiologic data, suggesting that the availability of key nutrients in the SAA pathway regulates fat storage pathways.

Journal

Mammalian GenomeSpringer Journals

Published: Jun 21, 2014

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off