Differential responses of white adipose tissue and brown adipose tissue to caloric restriction in rats

Okita, Naoyuki; Hayashida, Y.; Kojima, Yumiko; Fukushima, Mayumi; Yuguchi, Keiko; Mikami, Kentaro; Yamauchi, Akihito; Watanabe, Kyoko; Noguchi, Mituru; Nakamura, Megumi; Toda, Toshifusa; Higami, Yoshikazu

doi:10.1016/j.mad.2012.02.003

Cited by 49 publications

(57 citation statements)

References 63 publications

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“…These observations suggested that WAT derived from long‐lived strains of mice, that is, good‐quality WAT, can increase whole‐body lipid utilization. Recently, we proposed that Srebp‐1c‐induced activation of FA biosynthesis is one of the major mechanisms by which CR can remodel metabolism in WAT (Okita et al ., 2012; Chujo et al ., 2013). Previous studies clearly demonstrated that CR significantly enhanced whole‐body lipid utilization and increased endogenously synthesized FAs in WAT, but not in the liver (Bruss et al ., 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Male 5‐ to 7‐week‐old Wistar rats and their husbandry care and diet were as previously described (Okita et al ., 2012), and their use is described under additional experimental procedures in Data S1 (Supporting information). When the animals were euthanized, epididymal WAT samples were collected.…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed as described previously (Okita et al ., 2012). The methods are briefly described as additional experimental procedures in Data S1 (Supporting information).…”

Section: Methodsmentioning

confidence: 99%

“…The mtDNA content and CS activity were measured as previously described (Alp et al ., 1976; Okita et al ., 2012). The methods are briefly described as additional experimental procedures in Data S1 (Supporting information).…”

Section: Methodsmentioning

confidence: 99%

“…In particular, CR downregulated inflammatory gene expression in a GH/IGF‐1‐independent manner (Chujo et al ., 2013). In contrast, CR upregulated expression of Srebp‐1c (the mouse homolog of human SREBP‐1c) and its downstream target genes, especially those involved in FA biosynthesis, also in a GH/IGF‐1‐independent manner (Okita et al ., 2012; Chujo et al ., 2013). Moreover, CR significantly increased de novo FA biosynthesis in WAT but not in the liver (Bruss et al ., 2010).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed as described previously (Okita et al ., 2012). The methods are briefly described as additional experimental procedures in Data S1 (Supporting information).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

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WWP1 knockout in mice exacerbates obesity‐related phenotypes in white adipose tissue but improves whole‐body glucose metabolism

et al. 2020

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White adipose tissue (WAT) is important for maintenance of homeostasis, because it stores energy and secretes adipokines. The WAT of obese people demonstrates mitochondrial dysfunction, accompanied by oxidative stress, which leads to insulin resistance. WW domain‐containing E3 ubiquitin protein ligase 1 (WWP1) is a member of the HECT‐type E3 family of ubiquitin ligases and is associated with several diseases. Recently, we demonstrated that WWP1 is induced specifically in the WAT of obese mice, where it protects against oxidative stress. Here, we investigated the function of WWP1 in WAT of obese mice by analyzing the phenotype of Wwp1 knockout (KO) mice fed a high‐fat diet. The levels of oxidative stress markers were higher in obese WAT from Wwp1 KO mice. Moreover, Wwp1 KO mice had lower activity of citrate synthase, a mitochondrial enzyme. We also measured AKT phosphorylation in obese WAT and found lower levels in Wwp1 KO mice. However, plasma insulin level was low and glucose level was unchanged in obese Wwp1 KO mice. Moreover, both glucose tolerance test and insulin tolerance test were improved in obese Wwp1 KO mice. These findings indicate that WWP1 participates in the antioxidative response and mitochondrial function in WAT, but knockdown of WWP1 improves whole‐body glucose metabolism.

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Systemic depletion of WWP1 improves insulin sensitivity and lowers triglyceride content in the liver of obese mice

et al. 2023

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Obesity is a metabolic disorder associated with many diseases. WW domain‐containing E3 ubiquitin protein ligase 1 (WWP1) is a HECT‐type E3 ubiquitin ligase involved in several diseases. Recently, we found that the level of WWP1 is increased in white adipose tissue in a mouse model of obesity and that obese Wwp1 knockout (KO) mice exhibit improved whole‐body glucose metabolism. Here, to determine which insulin‐sensitive tissues contribute to this phenotype, we investigated the levels of several insulin signaling markers in white adipose tissue, liver, and skeletal muscle of Wwp1 KO mice, which were fed a normal or high‐fat diet and transiently treated with insulin. In obese Wwp1 KO mice, phosphorylated Akt levels were increased in the liver but not in white adipose tissue or skeletal muscle. Moreover, the weight and triglyceride content of the liver of obese Wwp1 KO mice were decreased. These results suggest that systemic deletion of WWP1 improves glucose metabolism via enhanced hepatic insulin signaling and suppressed hepatic fat accumulation. In summary, WWP1 participates in obesity‐related metabolic dysfunction and pathologies related to hepatic steatosis via suppressed insulin signaling.

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Differential responses of white adipose tissue and brown adipose tissue to caloric restriction in rats

Cited by 49 publications

References 63 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

WWP1 knockout in mice exacerbates obesity‐related phenotypes in white adipose tissue but improves whole‐body glucose metabolism

Systemic depletion of WWP1 improves insulin sensitivity and lowers triglyceride content in the liver of obese mice

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