A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis

Boström, Pontus; Wu, Jun; Jedrychowski, Mark P.; Korde, Anisha; Li, Ye; Lo, James C.; Rasbach, Kyle A.; Boström, Elisabeth A.; Choi, Jang Hyun; Long, Jonathan Z.; Kajimura, Shingo; Zingaretti, Maria Cristina; Vind, Birgitte F.; Tu, Hua; Cinti, Saverio; Højlund, Kurt; Gygi, Steven P.; Spiegelman, Bruce M.

doi:10.1038/nature10777

Cited by 4,014 publications

(5,241 citation statements)

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“…2012). Previous studies demonstrate increased FNDC5/irisin in response to chronic exercise (Bostrom et al.…”

Section: Discussionmentioning

confidence: 99%

“…FNDC5 is upregulated in response to acute exercise (Bostrom et al. 2012; Brenmoehl et al. 2014; Norheim et al.…”

Section: Introductionmentioning

confidence: 99%

“…Exercise‐induced expression of FNDC5/irisin in muscle has been shown to be dependent on increased PGC‐1 α (Bostrom et al. 2012; Brenmoehl et al. 2014; Norheim et al.…”

Section: Introductionmentioning

confidence: 99%

“…Following acute endurance exercise, FNDC5/irisin levels are significantly elevated, resulting in increased energy expenditure in mice (Bostrom et al. 2012; Brenmoehl et al. 2014; Norheim et al.…”

Section: Introductionmentioning

confidence: 99%

“…This increased energy expenditure is proposed to be mediated by increased browning of WAT via increased UCP1 levels (Bostrom et al. 2012; Wu et al. 2014).…”

Section: Introductionmentioning

confidence: 99%

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Increased FNDC5 is associated with insulin resistance in high fat-fed mice

et al. 2017

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FNDC5/irisin, has recently been identified as a novel protein that stimulates the “browning” of white adipose by inducing thermogenesis via increased uncoupling protein 1 (UCP1). We tested the hypothesis that high fat diet‐induced prediabetic mice would exhibit increased FNDC5 and this effect would be attenuated by chronic exercise. C57BL/6 mice were randomized into three groups for the 4 week intervention: Standard diet (Std, n = 12), High fat diet (HF, n = 14), or High fat diet and free access to a running wheel (HFEX, n = 14). Body weight, glucose, insulin, and the homeostatic model assessment of insulin resistance (HOMA‐IR) were greater in HF compared to Std and HFEX after the 4 week intervention. In support of our hypothesis, FNDC5 was higher in HF in both skeletal muscle and adipose compared to Std and was lower in adipose only in HFEX compared to HF mice. Following the same pattern, PGC‐1α was significantly higher in HF compared to Std in skeletal muscle and significantly lower in HFEX compared to HF in adipose. UCP1 was significantly lower in HFEX versus Std (in skeletal muscle) and versus HF (in adipose). HOMA‐IR was significantly correlated with FNDC5 protein levels in adipose. Increased FNDC5 in adipose and skeletal muscle may be a compensatory mechanism to offset high fat diet‐induced weight gain and insulin resistance by increasing energy expenditure.

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“…2012). Previous studies demonstrate increased FNDC5/irisin in response to chronic exercise (Bostrom et al.…”

Section: Discussionmentioning

confidence: 99%

“…FNDC5 is upregulated in response to acute exercise (Bostrom et al. 2012; Brenmoehl et al. 2014; Norheim et al.…”

Section: Introductionmentioning

confidence: 99%

“…Exercise‐induced expression of FNDC5/irisin in muscle has been shown to be dependent on increased PGC‐1 α (Bostrom et al. 2012; Brenmoehl et al. 2014; Norheim et al.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…This increased energy expenditure is proposed to be mediated by increased browning of WAT via increased UCP1 levels (Bostrom et al. 2012; Wu et al. 2014).…”

Section: Introductionmentioning

confidence: 99%

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