Leptin and mTOR: Partners in metabolism and inflammation

Maya‐Monteiro, Clarissa M.; Bozza, Patrı́cia T.

doi:10.4161/cc.7.12.6157

Cited by 100 publications

(81 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Besides, the activity of mTOR complex 1 is elevated in muscles from ob/ob mice. 28 In sharp contrast to the aforementioned results, recombinant leptin inhibits AMPK and consequently provokes the activation of mTOR in some cell types, for instance in hypothalamic neurons, 16 primary vascular smooth muscle cells, 29 hepatic stellate cells, 30 as well as peritoneal macrophages, 31,32 suggesting that leptin can inhibit autophagy as well. Accordingly, insulinproducing β cells from pancreatic islet exhibit increased autophagy in db/db mice.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 69%

Neuroendocrine regulation of autophagy by leptin

Malik

Mariño²,

BenYounès³

et al. 2011

Cell Cycle

View full text Add to dashboard Cite

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 69%

Neuroendocrine regulation of autophagy by leptin

Malik

Mariño²,

BenYounès³

et al. 2011

Cell Cycle

View full text Add to dashboard Cite

“…In addition, activation of mTORC1-S6K enhances the phosphorylation-dependent inhibition of AMPK by leptin (13). Interestingly, mTORC1 has also been found to mediate leptin action on lipid metabolism and inflammation in peripheral tissues (41,57). Taken together, these findings highlight the importance of the mTORC1 pathway in mediating the effects of leptin.…”

Section: E996 Hypothalamic Mtorc1 Regulates Energy Homeostasismentioning

confidence: 87%

Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis

Liu

2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

-Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight. mTOR integrates signals from a variety of "energy balancing" hormones such as leptin, insulin, and ghrelin, although its action varies in response to these distinct hormonal stimuli as well as across different neuronal populations. In this review, we summarize and highlight recent findings regarding the functional roles of mTOR complex 1 (mTORC1) in the hypothalamus specifically in its regulation of body weight, energy expenditure, and glucose/lipid homeostasis. Understanding the role and underlying mechanisms behind mTOR-related signaling in the brain will undoubtedly pave new avenues for future therapeutics and interventions that can combat obesity, insulin resistance, and diabetes. mTOR; hypothalamus; hormones; nutrients; energy homeostasis BALANCED FOOD INTAKE and energy expenditure are key to maintaining energy homeostasis, whereas impaired regulation of this balance leads to excessive weight gain and obesity. Food intake and energy expenditure are primarily controlled by the central nervous system (CNS), especially the hypothalamus, which acts as a key signaling hub linking CNS action to peripheral organ metabolism. Along with other nutrient sensors in different brain areas, the hypothalamus senses and integrates changes in circulating hormone and nutrient levels by relaying these peripheral signals to neuroendocrine cells, which signal behavioral and metabolic effectors to regulate whole body energy homeostasis (6,53,57,82).Extensive studies have been performed to explore the unique roles and distinct actions of several anatomically well-defined hypothalamic areas in the regulation of energy balance, including the arcuate nucleus (ARC) and ventromedial (VMH), dorsomedial (DMH), paraventricular (PVH), and lateral (LH) hypothalamus (74, 99). In the ARC, hormone and nutrient signals from the periphery induce activity changes of two subpopulations of neurons: an orexigenic population coexpressing the neurotransmitters neuropeptide Y (NPY) and agouti-related peptide (AgRP) and an anorexigenic population coexpressing proopiomelanocortin (POMC) and cocaine-and amphetamine-regulated transcript (CART). Numerous studies have demonstrated that POMC/CART and AgRP/NPY neurons have direct synaptic connections with some neuronal populations located in the VMH, DMH, PVH, and LH, all of which have profound effects on feeding behavior, energy expenditure, and glucose homeostasis (82).Leptin and insulin are two important hormonal regulators of peripheral energy homeostasis, which play critical roles in mediating CNS-controlled glucose, lipid, and energy metabolism by acting on the hypothalamus. Both the insulin and leptin receptors are widely expressed in the ARC, VMH, DMH, LH, and PVH, and together or independently these two ...

show abstract

“…18 Adipokines represent likely candidates to mediate, at least in part, the increased cancer risk and enhanced progression associated with adipocyte-derived secretory proteins. 19 Among the adipokines, leptin is the most intensively studied factor due to its involvement in tumor initiation, primary tumor growth, invasion, and metastasis.…”

Section: Discussionmentioning

confidence: 99%