Abstract
Summary Thermogenic brown and beige adipose tissues dissipate chemical energy as heat, and their thermogenic activities can combat obesity and diabetes. Herein the functional adaptations to cold of brown and beige adipose depots are examined using quantitative mitochondrial proteomics. We identify arginine/creatine metabolism as a beige adipose signature and demonstrate that creatine enhances respiration in beige-fat mitochondria when ADP is limiting. In murine beige fat, cold exposure stimulates mitochondrial creatine kinase activity and induces coordinated expression of genes associated with creatine metabolism. Pharmacological reduction of creatine levels decreases whole-body energy expenditure after administration of a β3-agonist and reduces beige and brown adipose metabolic rate. Genes of creatine metabolism are compensatorily induced when UCP1-dependent thermogenesis is ablated, and creatine reduction in Ucp1-deficient mice reduces core body temperature. These findings link a futile cycle of creatine metabolism to adipose tissue energy expenditure and thermal homeostasis. PaperClip.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 643-655 |
| Number of pages | 13 |
| Journal | Cell |
| Volume | 163 |
| Issue number | 3 |
| DOIs | |
| State | Published - Oct 22 2015 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
A Creatine-Driven Substrate Cycle Enhances Energy Expenditure and Thermogenesis in Beige Fat. / Kazak, Lawrence; Chouchani, Edward T.; Jedrychowski, Mark P.; Erickson, Brian K.; Shinoda, Kosaku; Cohen, Paul; Vetrivelan, Ramalingam; Lu, Gina Z.; Laznik-Bogoslavski, Dina; Hasenfuss, Sebastian C.; Kajimura, Shingo; Gygi, Steve P.; Spiegelman, Bruce M.
In: Cell, Vol. 163, No. 3, 22.10.2015, p. 643-655.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A Creatine-Driven Substrate Cycle Enhances Energy Expenditure and Thermogenesis in Beige Fat
AU - Kazak, Lawrence
AU - Chouchani, Edward T.
AU - Jedrychowski, Mark P.
AU - Erickson, Brian K.
AU - Shinoda, Kosaku
AU - Cohen, Paul
AU - Vetrivelan, Ramalingam
AU - Lu, Gina Z.
AU - Laznik-Bogoslavski, Dina
AU - Hasenfuss, Sebastian C.
AU - Kajimura, Shingo
AU - Gygi, Steve P.
AU - Spiegelman, Bruce M.
PY - 2015/10/22
Y1 - 2015/10/22
N2 - Summary Thermogenic brown and beige adipose tissues dissipate chemical energy as heat, and their thermogenic activities can combat obesity and diabetes. Herein the functional adaptations to cold of brown and beige adipose depots are examined using quantitative mitochondrial proteomics. We identify arginine/creatine metabolism as a beige adipose signature and demonstrate that creatine enhances respiration in beige-fat mitochondria when ADP is limiting. In murine beige fat, cold exposure stimulates mitochondrial creatine kinase activity and induces coordinated expression of genes associated with creatine metabolism. Pharmacological reduction of creatine levels decreases whole-body energy expenditure after administration of a β3-agonist and reduces beige and brown adipose metabolic rate. Genes of creatine metabolism are compensatorily induced when UCP1-dependent thermogenesis is ablated, and creatine reduction in Ucp1-deficient mice reduces core body temperature. These findings link a futile cycle of creatine metabolism to adipose tissue energy expenditure and thermal homeostasis. PaperClip.
AB - Summary Thermogenic brown and beige adipose tissues dissipate chemical energy as heat, and their thermogenic activities can combat obesity and diabetes. Herein the functional adaptations to cold of brown and beige adipose depots are examined using quantitative mitochondrial proteomics. We identify arginine/creatine metabolism as a beige adipose signature and demonstrate that creatine enhances respiration in beige-fat mitochondria when ADP is limiting. In murine beige fat, cold exposure stimulates mitochondrial creatine kinase activity and induces coordinated expression of genes associated with creatine metabolism. Pharmacological reduction of creatine levels decreases whole-body energy expenditure after administration of a β3-agonist and reduces beige and brown adipose metabolic rate. Genes of creatine metabolism are compensatorily induced when UCP1-dependent thermogenesis is ablated, and creatine reduction in Ucp1-deficient mice reduces core body temperature. These findings link a futile cycle of creatine metabolism to adipose tissue energy expenditure and thermal homeostasis. PaperClip.
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UR - http://www.scopus.com/inward/citedby.url?scp=84975757439&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2015.09.035
DO - 10.1016/j.cell.2015.09.035
M3 - Article
C2 - 26496606
AN - SCOPUS:84975757439
VL - 163
SP - 643
EP - 655
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -