Adipose mTORC2 is essential for sensory innervation in white adipose tissue and whole-body energy homeostasis

Frei, Irina C.; Weißenberger, Diana; Ritz, Danilo; Heusermann, Wolf; Colombi, Marco; Shimobayashi, Mitsugu; Hall, Michael N.

doi:10.1016/j.molmet.2022.101580

Cited by 13 publications

(2 citation statements)

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“…However, adipose tissue is not fully developed until six weeks of age and thus the impaired glucose uptake and DNL could be due to a developmental defect. To examine the role of mTORC2 in mature adipocytes in adult mice, we characterized inducible adipose-specific Rictor knockout mice (iAdRiKO: Rictor fl/fl Adipoq-CreER T2 ) (12). Rictor deletion was induced by tamoxifen injections at six- to eight-week of age and loss of RICTOR and mTORC2 activity were confirmed by immunoblotting ( Figures 1A-B ).…”

Section: Resultsmentioning

confidence: 99%

Hepatic mTORC2 compensates for loss of adipose mTORC2 in mediating energy storage and glucose homeostasis

Frei

Weißenberger

Müller

et al. 2022

Preprint

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Mammalian target of rapamycin complex 2 (mTORC2) is a protein kinase complex that plays an important role in energy homeostasis. Loss of adipose mTORC2 reduces lipogenic enzyme expression and de novo lipogenesis in adipose tissue. Adipose-specific mTORC2 knockout mice also displays triglyceride accumulation in the liver. However, the mechanism and physiological role of hepatic triglyceride accumulation upon loss of adipose mTORC2 are unknown. Here, we show that loss of adipose mTORC2 increases expression of de novo lipogenic enzymes in the liver, thereby causing accumulation of hepatic triglyceride and hypertriglyceridemia. Simultaneous inhibition of lipogenic enzymes in adipose tissue and liver by ablating mTORC2 in both tissues prevented accumulation of hepatic triglycerides and hypertriglyceridemia. However, loss of adipose and hepatic mTORC2 caused severe insulin resistance and glucose intolerance. Thus, our findings suggest that increased hepatic lipogenesis is a compensatory mechanism to cope with loss of lipogenesis in adipose tissue, and further suggest that mTORC2 in adipose tissue and liver plays a crucial role in maintaining whole-body energy homeostasis.

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Section: Resultsmentioning

confidence: 99%

Hepatic mTORC2 compensates for loss of adipose mTORC2 in mediating energy storage and glucose homeostasis

Frei

Weißenberger

Müller

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, MPZ+ nerves in mouse scWAT ran in parallel and in close proximity to IB4-marked vasculature, as evidenced by whole-depot confocal imaging ( Willows et al, 2021 ). Sensory neuropeptides exhibit vasomodulatory properties ( Brain et al, 1985 , Newby et al, 1999 ), as do sympathetic nerve products ( Nette et al, 2006 , Vatner et al, 1985 ), and thus likely both nerve types innervate adipose vasculature ( Frei et al, 2022 ). Additional CGRP (or another sensory marker) and MPZ/MBP costaining will be required to confirm whether myelinated sensory nerves innervate scWAT, and along which anatomical structures (such as vasculature) or cell types.…”

Section: Neuroanatomy Of the Sensory Nervous Systemmentioning

confidence: 99%