Adipocyte OGT governs diet-induced hyperphagia and obesity

Li, Min‐Dian; Vera, Nicholas B.; Yang, Yunfan; Zhang, Bichen; Ni, Weiming; Ziso-Qejvanaj, Enida; Ding, Sheng; Zhang, Kaisi; Yin, Ruonan; Wang, Simeng; Zhou, Xu; Fang, Ethan X.; Xu, Tian; Erion, Derek M.

doi:10.1038/s41467-018-07461-x

Cited by 49 publications

(48 citation statements)

References 59 publications

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“…On the other hand, OGT overexpression in adipose tissue inhibits stimulated lipolysis and promotes HFD-induced white fat accumulation and insulin resistance. Our previous result showed that constitutive adipose-specific Ogt-knockout mice are resistant to diet-induced obesity 43 . These findings demonstrate that adipose OGT is essential for the dynamic adaptation of adipose tissue to nutritional cues.…”

Section: Discussionmentioning

confidence: 99%

O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity

Yang

et al. 2020

Nat Commun

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Excessive visceral fat accumulation is a primary risk factor for metabolically unhealthy obesity and related diseases. The visceral fat is highly susceptible to the availability of external nutrients. Nutrient flux into the hexosamine biosynthetic pathway leads to protein posttranslational modification by O-linked β-N-acetylglucosamine (O-GlcNAc) moieties. O-GlcNAc transferase (OGT) is responsible for the addition of GlcNAc moieties to target proteins. Here, we report that inducible deletion of adipose OGT causes a rapid visceral fat loss by specifically promoting lipolysis in visceral fat. Mechanistically, visceral fat maintains a high level of O-GlcNAcylation during fasting. Loss of OGT decreases O-GlcNAcylation of lipid droplet-associated perilipin 1 (PLIN1), which leads to elevated PLIN1 phosphorylation and enhanced lipolysis. Moreover, adipose OGT overexpression inhibits lipolysis and promotes diet-induced obesity. These findings establish an essential role for OGT in adipose tissue homeostasis and indicate a unique potential for targeting O-GlcNAc signaling in the treatment of obesity.

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Section: Discussionmentioning

confidence: 99%

O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity

Yang

et al. 2020

Nat Commun

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“…It is worth noting that mice only respond to UA under an HFD, but not under a chow diet. This diet-dependent antiobesity effect is widely present in compound-treated normal mice [63,64], as well as in genetically modified mouse models [65]. The underlying mechanisms of these phenomena might be different and need further investigation.…”

Section: Plos Biologymentioning

confidence: 95%

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice

et al. 2020

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Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications.

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“…Results indicate that increased OGN levels function in the induction of adipocyte differentiation. The latter study showed that PPARγ is O-GlcNAcylated and that the O-GlcNAc modification is essential for the stability and transcriptional activity of PPARγ protein in adipose tissue [111,112]. O-GlcNAc is also involved in modulating the Wnt signaling pathway by negatively regulating β-catenin levels in the nucleus to decrease its transcriptional activity [113].…”

Section: Primary Cilia Inhibit Adipocyte Differentiation To Regulate mentioning

confidence: 97%

Potential Roles of O-GlcNAcylation in Primary Cilia- Mediated Energy Metabolism

Tian

Gomeshtapeh

2020

Biomolecules

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The primary cilium, an antenna-like structure on most eukaryotic cells, functions in transducing extracellular signals into intracellular responses via the receptors and ion channels distributed along it membrane. Dysfunction of this organelle causes an array of human diseases, known as ciliopathies, that often feature obesity and diabetes; this indicates the primary cilia’s active role in energy metabolism, which it controls mainly through hypothalamic neurons, preadipocytes, and pancreatic β-cells. The nutrient sensor, O-GlcNAc, is widely involved in the regulation of energy homeostasis. Not only does O-GlcNAc regulate ciliary length, but it also modifies many components of cilia-mediated metabolic signaling pathways. Therefore, it is likely that O-GlcNAcylation (OGN) plays an important role in regulating energy homeostasis in primary cilia. Abnormal OGN, as seen in cases of obesity and diabetes, may play an important role in primary cilia dysfunction mediated by these pathologies.

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Adipocyte OGT governs diet-induced hyperphagia and obesity

Cited by 49 publications

References 59 publications

O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity

O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity

Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice

Potential Roles of O-GlcNAcylation in Primary Cilia- Mediated Energy Metabolism

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