Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6

Tan, Chong Yew; Virtue, Samuel; Bidault, Guillaume; Dale, Martin; Hagen, R; Griffin, Julian L.; Vidal-Puig, António

doi:10.1016/j.celrep.2015.11.004

Cited by 56 publications

(55 citation statements)

References 22 publications

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“…Lipid metabolic genes (Cyp51, Idi1, Hsd17b7) were among the top regulated genes in Atg7 deficient stressed KC, and interestingly these genes were also found strongly induced in mitochondrial dysfunction models [62]. Further ELOVL6, which converts C16 to C18 FA and may regulate mitochondrial function by stearylation of the transferrin receptor [63] was induced in the knockouts and also by PQ.…”

Section: Discussionmentioning

confidence: 89%

Autophagy deficient keratinocytes display increased DNA damage, senescence and aberrant lipid composition after oxidative stress in vitro and in vivo

et al. 2017

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Autophagy allows cells fundamental adaptations to metabolic needs and to stress. Using autophagic bulk degradation cells can clear crosslinked macromolecules and damaged organelles that arise under redox stress. Accumulation of such debris results in cellular dysfunction and is observed in aged tissue and senescent cells. Conversely, promising anti-aging strategies aim at inhibiting the mTOR pathway and thereby activating autophagy, to counteract aging associated damage. We have inactivated autophagy related 7 (Atg7), an essential autophagy gene, in murine keratinocytes (KC) and have found in an earlier study that this resulted in increased baseline oxidative stress and reduced capacity to degrade crosslinked proteins after oxidative ultraviolet stress. To investigate whether autophagy deficiency would promote cellular aging, we studied how Atg7 deficient (KO) and Atg7 bearing cells (WT) would respond to stress induced by paraquat (PQ), an oxidant drug commonly used to induce cellular senescence.Atg7 deficient KC displayed increased prostanoid signaling and a pro- mitotic gene expression signature as compared to the WT. After exposure to PQ, both WT and KO cells showed an inflammatory and stress-related transcriptomic response. However, the Atg7 deficient cells additionally showed drastic DNA damage- and cell cycle arrest signaling. Indeed, DNA fragmentation and –oxidation were strongly increased in the stressed Atg7 deficient cells upon PQ stress but also after oxidizing ultraviolet A irradiation. Damage associated phosphorylated histone H2AX (γH2AX) foci were increased in the nuclei, whereas expression of the nuclear lamina protein lamin B1 was strongly decreased. Similarly, in both, PQ treated mouse tail skin explants and in UVA irradiated mouse tail skin, we found a strong increase in γH2AX positive nuclei within the basal layer of Atg7 deficient epidermis.Atg7 deficiency significantly affected expression of lipid metabolic genes. Therefore we performed lipid profiling of keratinocytes which demonstrated a major dysregulation of cellular lipid metabolism. We found accumulation of autophagy agonisitic free fatty acids, whereas triglyceride levels were strongly decreased. Together, our data show that in absence of Atg7/autophagy the resistance of keratinocytes to intrinsic and environmental oxidative stress was severely impaired and resulted in DNA damage, cell cycle arrest and a disturbed lipid phenotype, all typical for premature cell aging.

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Section: Discussionmentioning

confidence: 89%

Autophagy deficient keratinocytes display increased DNA damage, senescence and aberrant lipid composition after oxidative stress in vitro and in vivo

et al. 2017

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“…Taking into account that fatty acid oxidation provides fuel for thermogenesis, we measured several parameters related to this metabolic pathway. Immunohistochemical analysis of pWAT from the RSV + Q group showed an increase in transcriptional coactivator PGC‐1α, a potent inducer of mitochondrial biogenesis . In addition, the expression of Tfr1 was significantly reduced.…”

Section: Discussionmentioning

confidence: 99%

A combination of resveratrol and quercetin induces browning in white adipose tissue of rats fed an obesogenic diet

Arias

Picó

Macarulla

et al. 2016

Obesity

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Objective: To analyze whether a combination of quercetin (Q) and resveratrol (RSV) would induce a white adipose tissue (WAT) browning effect. Methods: Thirty-six rats were fed an obesogenic diet and divided into four groups: control, treated with RSV (15 mg/kg body weight/day; RSV group), treated with Q (30 mg/kg body weight/day; Q group), or treated with both polyphenols (RSV 1 Q group). Results: After 6 weeks, body and WAT weights were significantly reduced in the RSV 1 Q group. In perirenal WAT of the control, RSV, and Q groups, white unilocular adipocytes appeared in the majority of cells, while in the RSV 1 Q group numerous multilocular adipocytes with positive immunostaining for UCP1 were observed. The presence of UCP1 was confirmed by Western blot. This group also revealed increased mRNA levels of Cidea, Hocx9, Bmp4, Slc27a1, Pat2, Atgl, and Atp5d. Interscapular brown adipose tissue weight showed no differences between groups, but the Cidea mRNA level was increased in the RSV group, the Cox-2 mRNA level in the RSV 1 Q group, and UCP1 protein expression in the RSV and the RSV 1 Q groups. Conclusions: This study demonstrated that the RSV 1 Q combination produces a brown-like remodeling effect in perirenal WAT, as well as increased UCP1 protein expression in interscapular brown adipose tissue.

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“…A significant amount of functional brown fat is present in adult humans in the interscapular fat depot (Cypess and others 2009; van Marken Lichtenbelt and others 2009; Virtanen and others 2009), which shares characteristics of beige fat, rather than classical brown fat (Wu and others 2012). UCP1 expression declines with aging in rodents in subcutaneous white fat, suggesting that brown-like adipose tissue function (“beige” or “brite” adipocytes) is reduced with aging (Rogers and others 2012; Tan and others 2015). Additionally, brown fat itself may become dysfunctional with age (Saito and others 2009; Yamashita and others 1999; Yoneshiro and others 2011).…”

Section: Age-related Changes In Adipose Tissue Composition and Funmentioning

confidence: 99%

Aging and adipose tissue: potential interventions for diabetes and regenerative medicine

Palmer

Kirkland

2016

Experimental Gerontology

258

219

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Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies.

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Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6

Cited by 56 publications

References 22 publications

Autophagy deficient keratinocytes display increased DNA damage, senescence and aberrant lipid composition after oxidative stress in vitro and in vivo

Autophagy deficient keratinocytes display increased DNA damage, senescence and aberrant lipid composition after oxidative stress in vitro and in vivo

A combination of resveratrol and quercetin induces browning in white adipose tissue of rats fed an obesogenic diet

Aging and adipose tissue: potential interventions for diabetes and regenerative medicine

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