mTOR Pathway is Involved in Energy Homeostasis Regulation as a Part of the Gut–Brain Axis

Abstract

Mammalian, or mechanic, target of rapamycin (mTOR) signaling is a crucial factor in the regulation of the energy balance that functions as an energy sensor in the body. The present review explores how the mTOR/S6k intracellular pathway is involved in modulating the production of different signals such as ghrelin and nesfatin-1 in the gastrointestinal tract to regulate food intake and body weight. The role of gastric mTOR signaling in different physiological processes was studied in depth through different genetic models that allow the modulation of mTOR signaling in the stomach and specifically in gastric X/A type cells. It has been described that mTOR signaling in X/A-like gastric cells has a relevant role in the regulation of glucose and lipid homeostasis due to its interaction with different organs such as liver and adipose tissue. These findings highlight possible therapeutic strategies, with the gut–brain axis being one of the most promising targets in the treatment of obesity.

Integration of Nutrient Sensing in Fish Hypothalamus

“…Several studies demonstrate increased mTOR mRNA abundance and phosphorylation status in hypothalamus after a rise in the levels of leucine in mammals (Hu et al, 2016;Pena-Leon et al, 2020). In contrast, the effects of fatty acid or glucose on central mTOR are mostly unknown (André and Cota, 2012).…”

Lysine Deprivation Regulates Npy Expression via GCN2 Signaling Pathway in Mandarin Fish (Siniperca chuatsi)

“…In eukaryotes, two remarkable systems governing amino acid sensing are the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway and the general control nonderepressible 2 (GCN2) signaling pathway, which are integrated to response to fluctuating amino acid levels in supporting protein synthesis and maintaining metabolic homeostasis. Numerous studies concentrate on the influences of mTORC1 signaling in growth performance and amino acid metabolism [ 5 , 6 , 7 , 8 ]. However, there is a shortage in the literature regarding the effect of GCN2 signaling on these processes.…”

Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4

“…Since mTOR has been shown to positively regulate adipogenesis and lipogenesis while inhibiting lipolysis, fatty acid oxidation and ketogenesis ( 17 ), we performed adipogenesis and glycerol assays in 3T3-L1 adipocytes. We constructed lentiviral vector expressing miRNA inhibitors (pLV-locker 221, pLV-locker 222, pLV-locker control) and miRNA mimics (pLV 221, pLV 222, pLV control).…”