A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance
Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supp...
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| Veröffentlicht in: | Cell metabolism 2009-04, Vol.9 (4), p.311-326 |
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| creator | Newgard, Christopher B. An, Jie Bain, James R. Muehlbauer, Michael J. Stevens, Robert D. Lien, Lillian F. Haqq, Andrea M. Shah, Svati H. Arlotto, Michelle Slentz, Cris A. Rochon, James Gallup, Dianne Ilkayeva, Olga Wenner, Brett R. Yancy, William S. Eisenson, Howard Musante, Gerald Surwit, Richard S. Millington, David S. Butler, Mark D. Svetkey, Laura P. |
| description | Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets. Despite having reduced food intake and a low rate of weight gain equivalent to the SC group, HF/BCAA rats were as insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1
Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance. |
| doi_str_mv | 10.1016/j.cmet.2009.02.002 |
| format | Article |
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Ser307 and by accumulation of multiple acylcarnitines in muscle, and it was reversed by the mTOR inhibitor, rapamycin. Our findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance.</description><identifier>ISSN: 1550-4131</identifier><identifier>EISSN: 1932-7420</identifier><identifier>DOI: 10.1016/j.cmet.2009.02.002</identifier><identifier>PMID: 19356713</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acids, Branched-Chain - metabolism ; Animals ; Cytokines - metabolism ; Demography ; Dietary Fats - administration & dosage ; Dietary Fats - pharmacology ; Dietary Supplements ; Feeding Behavior - drug effects ; Female ; Hormones - metabolism ; Humans ; HUMDISEASE ; Insulin - metabolism ; Insulin Resistance - physiology ; Male ; Mass Spectrometry ; Metabolome ; Metabolomics ; Middle Aged ; Obesity - metabolism ; Rats ; Rats, Wistar ; Signal Transduction - drug effects ; Thinness - metabolism</subject><ispartof>Cell metabolism, 2009-04, Vol.9 (4), p.311-326</ispartof><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-962eaf24bcdd40ad4afdc4bfae72c1d63984b95daadd4f8ab4351c797b645c343</citedby><cites>FETCH-LOGICAL-c453t-962eaf24bcdd40ad4afdc4bfae72c1d63984b95daadd4f8ab4351c797b645c343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1550413109000400$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19356713$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Newgard, Christopher B.</creatorcontrib><creatorcontrib>An, Jie</creatorcontrib><creatorcontrib>Bain, James R.</creatorcontrib><creatorcontrib>Muehlbauer, Michael J.</creatorcontrib><creatorcontrib>Stevens, Robert D.</creatorcontrib><creatorcontrib>Lien, Lillian F.</creatorcontrib><creatorcontrib>Haqq, Andrea M.</creatorcontrib><creatorcontrib>Shah, Svati H.</creatorcontrib><creatorcontrib>Arlotto, Michelle</creatorcontrib><creatorcontrib>Slentz, Cris A.</creatorcontrib><creatorcontrib>Rochon, James</creatorcontrib><creatorcontrib>Gallup, Dianne</creatorcontrib><creatorcontrib>Ilkayeva, Olga</creatorcontrib><creatorcontrib>Wenner, Brett R.</creatorcontrib><creatorcontrib>Yancy, William S.</creatorcontrib><creatorcontrib>Eisenson, Howard</creatorcontrib><creatorcontrib>Musante, Gerald</creatorcontrib><creatorcontrib>Surwit, Richard S.</creatorcontrib><creatorcontrib>Millington, David S.</creatorcontrib><creatorcontrib>Butler, Mark D.</creatorcontrib><creatorcontrib>Svetkey, Laura P.</creatorcontrib><title>A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance</title><title>Cell metabolism</title><addtitle>Cell Metab</addtitle><description>Metabolomic profiling of obese versus lean humans reveals a branched-chain amino acid (BCAA)-related metabolite signature that is suggestive of increased catabolism of BCAA and correlated with insulin resistance. To test its impact on metabolic homeostasis, we fed rats on high-fat (HF), HF with supplemented BCAA (HF/BCAA), or standard chow (SC) diets. Despite having reduced food intake and a low rate of weight gain equivalent to the SC group, HF/BCAA rats were as insulin resistant as HF rats. Pair-feeding of HF diet to match the HF/BCAA animals or BCAA addition to SC diet did not cause insulin resistance. Insulin resistance induced by HF/BCAA feeding was accompanied by chronic phosphorylation of mTOR, JNK, and IRS1
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| subjects | Amino Acids, Branched-Chain - metabolism Animals Cytokines - metabolism Demography Dietary Fats - administration & dosage Dietary Fats - pharmacology Dietary Supplements Feeding Behavior - drug effects Female Hormones - metabolism Humans HUMDISEASE Insulin - metabolism Insulin Resistance - physiology Male Mass Spectrometry Metabolome Metabolomics Middle Aged Obesity - metabolism Rats Rats, Wistar Signal Transduction - drug effects Thinness - metabolism |
| title | A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance |
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