Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation

Jieun Lee; Jessica M. Ellis; Michael J. Wolfgang

doi:10.1016/j.celrep.2014.12.023

Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation

Jieun Lee, Jessica M. Ellis, Michael J. Wolfgang

School of Medicine

Research output: Contribution to journal › Article › peer-review

101 Scopus citations

Abstract

To understand the contribution of adipose tissue fatty acid oxidation to whole-body metabolism, we generated mice with an adipose-specific knockout of carnitine palmitoyltransferase 2 (CPT2^A-/-), an obligate step in mitochondrial long-chain fatty acid oxidation. CPT2^A-/- mice became hypothermic after an acute cold challenge, and CPT2^A-/- brown adipose tissue (BAT) failed to upregulate thermogenic genes in response to agonist-induced stimulation. The adipose-specific loss of CPT2 resulted in diet-dependent changes in adiposity but did not result in changes in body weight on low- or high-fat diets. Additionally, CPT2^A-/- mice had suppressed high-fat diet-induced oxidative stress and inflammation in visceral white adipose tissue (WAT); however, high-fat diet-induced glucose intolerance was not improved. These data show that fatty acid oxidation is required for cold-induced thermogenesis in BAT and high-fat diet-induced oxidative stress and inflammation in WAT.

Original language	English (US)
Pages (from-to)	266-279
Number of pages	14
Journal	Cell Reports
Volume	10
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2014.12.023
State	Published - Jan 13 2015

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2014.12.023

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title = "Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation",

abstract = "To understand the contribution of adipose tissue fatty acid oxidation to whole-body metabolism, we generated mice with an adipose-specific knockout of carnitine palmitoyltransferase 2 (CPT2A-/-), an obligate step in mitochondrial long-chain fatty acid oxidation. CPT2A-/- mice became hypothermic after an acute cold challenge, and CPT2A-/- brown adipose tissue (BAT) failed to upregulate thermogenic genes in response to agonist-induced stimulation. The adipose-specific loss of CPT2 resulted in diet-dependent changes in adiposity but did not result in changes in body weight on low- or high-fat diets. Additionally, CPT2A-/- mice had suppressed high-fat diet-induced oxidative stress and inflammation in visceral white adipose tissue (WAT); however, high-fat diet-induced glucose intolerance was not improved. These data show that fatty acid oxidation is required for cold-induced thermogenesis in BAT and high-fat diet-induced oxidative stress and inflammation in WAT.",

author = "Jieun Lee and Ellis, {Jessica M.} and Wolfgang, {Michael J.}",

note = "Funding Information: The authors would like to thank Susan Aja for assistance with the metabolic cage studies, Natasha Zachara for reagents, and G. W. Wong for helpful discussions. This work was supported in part by a NIH grant R01NS072241 to M.J.W. This work utilized Metabolomics Core Services supported by grant U24 DK097153 of NIH Common Funds Project to the University of Michigan. Publisher Copyright: {\textcopyright} 2015 The Authors.",

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doi = "10.1016/j.celrep.2014.12.023",

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N2 - To understand the contribution of adipose tissue fatty acid oxidation to whole-body metabolism, we generated mice with an adipose-specific knockout of carnitine palmitoyltransferase 2 (CPT2A-/-), an obligate step in mitochondrial long-chain fatty acid oxidation. CPT2A-/- mice became hypothermic after an acute cold challenge, and CPT2A-/- brown adipose tissue (BAT) failed to upregulate thermogenic genes in response to agonist-induced stimulation. The adipose-specific loss of CPT2 resulted in diet-dependent changes in adiposity but did not result in changes in body weight on low- or high-fat diets. Additionally, CPT2A-/- mice had suppressed high-fat diet-induced oxidative stress and inflammation in visceral white adipose tissue (WAT); however, high-fat diet-induced glucose intolerance was not improved. These data show that fatty acid oxidation is required for cold-induced thermogenesis in BAT and high-fat diet-induced oxidative stress and inflammation in WAT.

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Adipose fatty acid oxidation is required for thermogenesis and potentiates oxidative stress-induced inflammation

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