Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS

Nisoli, Enzo; Tonello, Cristina; Cardile, Annalisa; Cozzi, Valeria; Bracale, Renata; Tedesco, Laura; Falcone, Sestina; Valerio, Alessandra; Cantoni, Orazio; Clementi, Emilio; Moncada, Salvador; Carruba, Michele O.

doi:10.1126/science.1117728

Cited by 987 publications

(877 citation statements)

References 24 publications

Supporting

Mentioning

805

Contrasting

Unclassified

Order By: Relevance

“…In various reports, CR enhanced mitochondrial biogenesis in several tissues (Nisoli et al ., 2005; Finck & Kelly, 2006). Two long‐lived strains, FIRKO and β/β mice, showed, compared with WT mice, decreased adiposity and enhanced mitochondrial biogenesis in WAT (Chiu et al ., 2004; Katic et al ., 2007).…”

Section: Resultsmentioning

confidence: 99%

“…These findings are inconsistent with a previous report that CR enhanced mitochondrial biogenesis in various tissues, including WAT and liver (Nisoli et al ., 2005). In contrast to that, however, certain reports suggested that CR did not induce mitochondrial biogenesis or increase mitochondrial content (Hempenstall et al ., 2012; Lanza et al ., 2012).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

et al. 2017

View full text Add to dashboard Cite

SummaryCaloric restriction (CR) can delay onset of several age‐related pathophysiologies and extend lifespan in various species, including rodents. CR also induces metabolic remodeling involved in activation of lipid metabolism, enhancement of mitochondrial biogenesis, and reduction of oxidative stress in white adipose tissue (WAT). In studies using genetically modified mice with extended lifespans, WAT characteristics influenced mammalian lifespans. However, molecular mechanisms underlying CR‐associated metabolic remodeling of WAT remain unclear. Sterol regulatory element‐binding protein‐1c (Srebp‐1c), a master transcription factor of fatty acid (FA) biosynthesis, is responsible for the pathogenesis of fatty liver (steatosis). Our study showed that, under CR conditions, Srebp‐1c enhanced mitochondrial biogenesis via increased expression of peroxisome proliferator‐activated receptor gamma coactivator‐1α (Pgc‐1α) and upregulated expression of proteins involved in FA biosynthesis within WAT. However, via Srebp‐1c, most of these CR‐associated metabolic alterations were not observed in other tissues, including the liver. Moreover, our data indicated that Srebp‐1c may be an important factor both for CR‐associated suppression of oxidative stress, through increased synthesis of glutathione in WAT, and for the prolongevity action of CR. Our results strongly suggested that Srebp‐1c, the primary FA biosynthesis‐promoting transcriptional factor implicated in fatty liver disease, is also the food shortage‐responsive factor in WAT. This indicated that Srebp‐1c is a key regulator of metabolic remodeling leading to the beneficial effects of CR.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

et al. 2017

View full text Add to dashboard Cite

show abstract

“…It has been reported that the mitochondrial function is adapted in response to calorie restriction and this adaptation is critically involved in lifespan extension (Anderson et al 2008). Calorie restriction has been shown to activate PGC-1α (Nisoli et al 2005;Anderson et al 2008;Anderson and Weindruch 2009) and it may be an effective strategy in delaying aging-induced cellular phenotypes in skeletal muscle (McKiernan et al 2010). PGC-1α is critical for the adaptation of muscle mitochondriogenesis to exercise which activates the expression of NRF-1 which in turn, activates TFAM, a factor required for the duplication of mitochondrial DNA (Hood 2001).…”

Section: Discussionmentioning

confidence: 99%

Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1α to exercise training

Derbré

Gómez-Cabrera

Nascimento

et al. 2011

AGE

112

View full text Add to dashboard Cite

Low mitochondriogenesis is critical to explain loss of muscle function in aging and in the development of frailty. The aim of this work was to explain the mechanism by which mitochondriogenesis is decreased in aging and to determine to which extent it may be prevented by exercise training. We used aged rats and compared them with peroxisome proliferator-activated receptor-γ coactivator-1α deleted mice (PGC-1α KO). PGC-1α KO mice showed a significant decrease in the mitochondriogenic pathway in muscle. In aged rats, we found a loss of exercise-induced expression of PGC-1α, nuclear respiratory factor-1 (NRF-1), and of cytochrome C. Thus muscle mitochondriogenesis, which is activated by exercise training in young animals, is not in aged or PGC-1α KO ones. Other stimuli to increase PGC-1α synthesis apart from exercise training, namely cold induction or thyroid hormone treatment, were effective in young rats but not in aged ones. To sum up, the low mitochondrial biogenesis associated with aging may be due to the lack of response of PGC-1α to different stimuli. Aged rats behave as PGC-1α KO mice. Results reported here highlight the role of PGC-1α in the loss of mitochondriogenesis associated with aging and point to this important transcriptional coactivator as a target for pharmacological interventions to prevent age-associated sarcopenia.

show abstract

“…Likewise, blocking Sirt1 function results in decreased NO bioavailability and inhibited endothelium-dependent vasorelaxation (Mattagajasingh et al 2007). Interestingly, eNOS has also been implicated in the regulation of the expression of Sirt1 (Nisoli et al 2005), and NO itself could act as an inducer of Sirt1 activity in endothelium (Ota et al 2010).…”

mentioning

confidence: 99%

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Tomada

Almeida

et al. 2011

AGE

View full text Add to dashboard Cite

Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD + -dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.

show abstract

Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS

Cited by 987 publications

References 24 publications

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction

Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1α to exercise training

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Contact Info

Product

Resources

About