Exercise as a new physiological stimulus for brown adipose tissue activity

Matteis, Rita De; Lucertini, Francesco; Guescini, Michele; Polidori, Emanuela; Zeppa, Sabrina Donati; Stocchi, Vilberto; Cinti, Saverio; Cuppini, Riccardo

doi:10.1016/j.numecd.2012.01.013

Cited by 178 publications

(156 citation statements)

References 34 publications

(42 reference statements)

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“…Exercise enhanced the appearance of putative brown adipocyte progenitor cells in brown AT [40] and was described as novel physiological stimulus for browning of visceral fat in mice after controlled treadmill running [41] and free wheel running [21]. Several lines of evidence have suggested that bone morphogenetic proteins (BMP) induce adipose cell fate determination in mammalian cells (reviewed in [42]).…”

Section: Discussionmentioning

confidence: 99%

Evidence against a beneficial effect of irisin in humans

Raschke¹,

Elsen²,

Romacho³

et al. 2013

Exp Clin Endocrinol Diabetes

126

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Brown adipose tissue has gained interest as a potential target to treat obesity and metabolic diseases. Irisin is a newly identified hormone secreted from skeletal muscle enhancing browning of white fat cells, which improves systemic metabolism by increasing energy expenditure in mice. The discovery of irisin raised expectations of its therapeutic potential to treat metabolic diseases. However, the effect of irisin in humans is unclear. Analyses of genomic DNA, mRNA and expressed sequence tags revealed that FNDC5, the gene encoding the precursor of irisin, is present in rodents and most primates, but shows in humans a mutation in the conserved start codon ATG to ATA. HEK293 cells transfected with a human FNDC5 construct with ATA as start codon resulted in only 1% full-length protein compared to human FNDC5 with ATG. Additionally, in vitro contraction of primary human myotubes by electrical pulse stimulation induced a significant increase in PGC1a mRNA expression. However, FNDC5 mRNA level was not altered. FNDC5 mRNA expression in muscle biopsies from two different human exercise studies was not changed by endurance or strength training. Preadipocytes isolated from human subcutaneous adipose tissue exhibited differentiation to brite human adipocytes when incubated with bone morphogenetic protein (BMP) 7, but neither recombinant FNDC5 nor irisin were effective. In conclusion, our findings suggest that it is rather unlikely that the beneficial effect of irisin observed in mice can be translated to humans.

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Section: Discussionmentioning

confidence: 99%

Evidence against a beneficial effect of irisin in humans

Raschke¹,

Elsen²,

Romacho³

et al. 2013

Exp Clin Endocrinol Diabetes

126

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show abstract

“…In this context, it has been reported that chronic endurance exercise (9,10) has the ability to promote the expression of thermogenic genes in white adipocytes ("browning" of the WAT) and increase whole-body energy expenditure. Such effects have been proposed to be induced by a myokine released during exercise (irisin) derived from the cleavage of fibronectin domain-containing protein 5 (FNDC5) that promotes browning of the SC WAT (9).…”

mentioning

confidence: 99%

Thermogenic Capacity Is Antagonistically Regulated in Classical Brown and White Subcutaneous Fat Depots by High Fat Diet and Endurance Training in Rats

Bikopoulos

Hung

et al. 2014

Journal of Biological Chemistry

164

206

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Background: Brown adipose tissue (BAT) is important for cold-and diet-induced thermogenesis. Results: Obesity and chronic exercise antagonistically regulate thermogenic capacity of BAT and subcutaneous white fat (SC WAT). Conclusion: Endurance exercise reduces thermogenic capacity in classical BAT while increasing it in the SC WAT. Significance: Browning of the SC WAT may be potentially used to treat obesity.

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“…Both white and brown adipose cells express metabolite receptors and transporters, which may act as sensors of their metabolic environment. Proton-linked monocarboxylate transporters (MCTs) (12), which drive lactate, pyruvate, and ketone body transport across plasma membranes, are present on the surface of rodent (13)(14)(15) and human (16) adipocytes. Notably, the MCT1 isoform, mainly involved in lactate import into cells, strongly increases in BAT after exercise (15).…”

mentioning

confidence: 99%

“…Proton-linked monocarboxylate transporters (MCTs) (12), which drive lactate, pyruvate, and ketone body transport across plasma membranes, are present on the surface of rodent (13)(14)(15) and human (16) adipocytes. Notably, the MCT1 isoform, mainly involved in lactate import into cells, strongly increases in BAT after exercise (15). WAT adipocytes also express the G-proteincoupled receptors (GPRs) GPR81 and GPR109A, which are activated by lactate and the ketone body b-hydroxybutyrate (bHB), respectively (17).…”

mentioning

confidence: 99%

Browning of White Adipose Cells by Intermediate Metabolites: An Adaptive Mechanism to Alleviate Redox Pressure

et al. 2014

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The presence of brown adipose tissue (BAT) in human adults opens attractive perspectives to treat metabolic disorders. Indeed, BAT dissipates energy as heat via uncoupling protein (UCP)1. Brown adipocytes are located in specific deposits or can emerge among white fat through the so-called browning process. Although numerous inducers have been shown to drive this process, no study has investigated whether it could be controlled by specific metabolites. Here, we show that lactate, an important metabolic intermediate, induces browning of murine white adipose cells with expression of functional UCP1. Lactate-induced browning also occurs in human cells and in vivo. Lactate controls Ucp1 expression independently of hypoxia-inducible factor-1a and PPARa pathways but requires active PPARg signaling. We demonstrate that the lactate effect on Ucp1 is mediated by intracellular redox modifications as a result of lactate transport through monocarboxylate transporters. Further, the ketone body b-hydroxybutyrate, another metabolite that impacts redox state, is also a strong browning inducer. Because this redox-dependent increase in Ucp1 expression promotes an oxidative phenotype with mitochondria, browning appears as an adaptive mechanism to alleviate redox pressure. Our findings open new perspectives for the control of adipose tissue browning and its physiological relevance.

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Exercise as a new physiological stimulus for brown adipose tissue activity

Cited by 178 publications

References 34 publications

Evidence against a beneficial effect of irisin in humans

Evidence against a beneficial effect of irisin in humans

Thermogenic Capacity Is Antagonistically Regulated in Classical Brown and White Subcutaneous Fat Depots by High Fat Diet and Endurance Training in Rats

Browning of White Adipose Cells by Intermediate Metabolites: An Adaptive Mechanism to Alleviate Redox Pressure

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