Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver

Martínez–López, Nuria; García-Macia, Marina; Sahu, Srabani; Athonvarangkul, Diana; Liebling, Emily J.; Merlo, Paola; Cecconi, Francesco; Schwartz, Gary J.; Singh, Rajat

doi:10.1016/j.cmet.2015.10.008

Cited by 253 publications

(245 citation statements)

References 34 publications

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“…41 The apparent contradiction of this observation with our current findings will deserve further research. However, the complex intracellular machinery associated with thermogenic activation in brown adipocytes (including UCP1 protein increase) is known to be minimally developed in such a very short-time cold exposure setting and, in fact, shivering is the major response to very short-time acute exposure to cold.…”

Section: Discussioncontrasting

confidence: 60%

Thermogenic activation represses autophagy in brown adipose tissue

et al. 2016

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Section: Discussioncontrasting

confidence: 60%

Thermogenic activation represses autophagy in brown adipose tissue

et al. 2016

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“…Induction of lipophagy is part of a complex cellular and physiological response to several stimuli such as starvation [5], β-adrenergic stimulation [29], fatty acid loading [5], and cold exposure [30 ▪▪ ]. Accordingly, negative (Fig.…”

Section: Regulation Of Lipophagymentioning

confidence: 99%

“…Though mTOR inhibition is not a very specific way to enhance lipophagy, it has been shown to do so in-vivo in several contexts. Martinez-Lopez et al [30 ▪▪ ] showed induction of lipophagy specifically in the brain with rapamycin reduced lipid accumulation in an autophagy-dependent fashion. Remarkably, using rapamycin to drive lipophagy or ATG7 silencing to block lipophagy was sufficient to drive efferent neural signaling to induce matching lipophagic responses in brown adipose tissue and liver.…”

Section: Regulation Of Lipophagymentioning

confidence: 99%

Classical and alternative roles for autophagy in lipid metabolism

Zhang

Evans

Jeong

et al. 2018

Current Opinion in Lipidology

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Purpose of review Intracellular lipid metabolism is a complex interplay of exogenous lipid handling, trafficking, storage, lipolysis, and export. Recent work has implicated the cellular degradative process called autophagy in several aspects of lipid metabolism. We will discuss both the classical and novel roles of autophagy and the autophagic machinery in this setting. Recent findings The delivery of lipid droplets to lysosomes for hydrolysis, named lipophagy, was the first described functional role for autophagy in lipid metabolism. The molecular machinery and regulation of this selective form of macroautophagy is beginning to be discovered and has the potential to shed enormous light on intracellular lipolysis. Yet, the autophagic machinery appears to also be coopted for alternative roles that include interaction with cytosolic lipolysis pathways, supply and expansion of lipid droplets, and lipoprotein trafficking. Additionally, lesser studied forms of autophagy called microautophagy and chaperone-mediated autophagy have distinct roles in lipid handling that also intersect with classical macroautophagy. The integration of current knowledge in these areas into a holistic understanding of intracellular lipid metabolism will be a goal of this review. Summary As the field of autophagy has evolved and expanded to include functional roles in various aspects of cellular degradation, so has its role in intracellular lipid metabolism. Understanding the mechanisms underlying these classical and alternative roles of autophagy will not only enhance our knowledge in lipid biology but also provide new avenues of translation to human lipid disorders.

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“…Elevated T3 in ARC appeared to accelerate UCP2-dependent mitochondrial uncoupling in neuropeptide Y/AgRP neurons, leading to consequent rebound feeding following food deprivation [74]. The observation that TH regulates POMC expression in the ARC may be relevant for cold-induced BAT thermogenesis as a recent study showed that cold exposure induces autophagy in hypothalamic POMC neurons, which is necessary to activate lipophagy in BAT and the liver through the sympathetic network favoring cold-induced thermogenesis [75]. …”

Section: Systemic Effects Of Intrahypothalamic Thmentioning

confidence: 99%

TRH Neurons and Thyroid Hormone Coordinate the Hypothalamic Response to Cold

Zhi¹,

Boelen²,

Kalsbeek³

et al. 2018

Eur Thyroid J

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Thyroid hormone (TH) plays a key role in regulating body temperature in mammals. Cold exposure stimulates the hypothalamus-pituitary-thyroid (HPT) axis at the hypothalamic level by activating hypophysiotropic thyrotropin-releasing hormone (TRH)-producing neurons, ultimately resulting in increased plasma TH concentrations. Importantly, the local TH metabolism within various cold-responsive organs enables tissue-specific action of TH on heat production and adaption to cold independently of the circulating TH levels. In addition to these neuroendocrine effects, TRH neurons in the hypothalamus also have neural connections with brown adipose tissue (BAT), probably contributing to regulation of thermogenesis by the autonomic nervous system. Recent studies have demonstrated that intrahypothalamic TH has profound metabolic effects on BAT, the liver, and the heart that are mediated via the autonomic nervous system. These effects originate in various hypothalamic nuclei, including the paraventricular nucleus (PVN), the ventromedial nucleus, and recently reported neurons in the anterior hypothalamic area, indicating a potential central function for TH on thermoregulation. Finally, although robust stimulation of the thermogenic program in BAT was shown upon TH administration in the ventromedial hypothalamus, the physiological relevance of these neurally mediated effects of TH is unclear at present. This review provides an overview of studies reporting the role of TH in cold defense, with a focus on recent literature evidencing the centrally mediated effects of TRH and TH.

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Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver

Cited by 253 publications

References 34 publications

Thermogenic activation represses autophagy in brown adipose tissue

Thermogenic activation represses autophagy in brown adipose tissue

Classical and alternative roles for autophagy in lipid metabolism

TRH Neurons and Thyroid Hormone Coordinate the Hypothalamic Response to Cold

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