scholarly journals Fatty Acid Synthase Inhibitors Modulate Energy Balance via Mammalian Target of Rapamycin Complex 1 Signaling in the Central Nervous System

Diabetes ◽  
2008 ◽  
Vol 57 (12) ◽  
pp. 3231-3238 ◽  
Author(s):  
Karine Proulx ◽  
Daniela Cota ◽  
Stephen C. Woods ◽  
Randy J. Seeley
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Fatty Acid ◽  
Energy Balance ◽  
Fatty Acid Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
The Central Nervous System

scholarly journals C75, a Fatty Acid Synthase Inhibitor, Reduces Food Intake via Hypothalamic AMP-activated Protein Kinase

2004 ◽  
Vol 279 (19) ◽  
pp. 19970-19976 ◽  
Author(s):  
Eun-Kyoung Kim ◽  
Ian Miller ◽  
Susan Aja ◽  
Leslie E. Landree ◽  
Michael Pinn ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Fatty Acid ◽  
Energy Balance ◽  
Protein Kinase ◽  
Food Intake ◽  
Fatty Acid Synthase ◽  
Α Subunit ◽  
Compound C ◽  
Amp Activated Protein Kinase

Energy homeostasis and feeding are regulated by the central nervous system. C75, a fatty acid synthase (FAS) inhibitor, causes weight loss and anorexia, implying a novel central nervous system pathway(s) for sensing energy balance. AMP-activated protein kinase (AMPK), a sensor of peripheral energy balance, is phosphorylated and activated when energy sources are low. Here, we identify a role for hypothalamic AMPK in the regulation of feeding behavior and in mediating the anorexic effects of C75. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an activator of AMPK, increased food intake, whereas compound C, an inhibitor of AMPK, decreased food intake. C75 rapidly reduced the level of the phosphorylated AMPK α subunit (pAMPKα) in the hypothalamus, even in fasted mice that had elevated hypothalamic pAMPKα levels. Furthermore, AICAR reversed both the C75-induced anorexia and the decrease in hypothalamic pAMPKα levels. C75 elevated hypothalamic neuronal ATP levels, which may contribute to the mechanism by which C75 decreased AMPK activity. C75 reduced the levels of pAMPKα and phosphorylated cAMP response element-binding protein (pCREB) in the arcuate nucleus neurons of the hypothalamus, suggesting a mechanism for the reduction in NPY expression seen with C75 treatment. These data indicate that modulation of FAS activity in the hypothalamus can alter energy perception via AMPK, which functions as a physiological energy sensor in the hypothalamus.

scholarly journals Circulating insulin stimulates fatty acid retention in white adipose tissue via KATPchannel activation in the central nervous system only in insulin-sensitive mice

2011 ◽  
Vol 52 (9) ◽  
pp. 1712-1722 ◽  
Author(s):  
Claudia P. Coomans ◽  
Janine J. Geerling ◽  
Bruno Guigas ◽  
Anita M. van den Hoek ◽  
Edwin T. Parlevliet ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
White Adipose Tissue ◽  
The Central Nervous System

scholarly journals Tachykinin-1 in the Central Nervous System Regulates Adiposity in Rodents

Endocrinology ◽  
2015 ◽  
Vol 156 (5) ◽  
pp. 1714-1723 ◽  
Author(s):  
Chitrang Trivedi ◽  
Xiaoye Shan ◽  
Yi-Chun Loraine Tung ◽  
Dhiraj Kabra ◽  
Jenna Holland ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Energy Balance ◽  
Mass Gain ◽  
Neural System ◽  
Negative Energy ◽  
Microarray Gene Expression ◽  
Ghrelin Receptor ◽  
Ovariectomized Mice ◽  
The Central Nervous System

Ghrelin is a circulating hormone that targets the central nervous system to regulate feeding and adiposity. The best-characterized neural system that mediates the effects of ghrelin on energy balance involves the activation of neuropeptide Y/agouti-related peptide neurons, expressed exclusively in the arcuate nucleus of the hypothalamus. However, ghrelin receptors are expressed in other neuronal populations involved in the control of energy balance. We combined laser capture microdissection of several nuclei of the central nervous system expressing the ghrelin receptor (GH secretagoge receptor) with microarray gene expression analysis to identify additional neuronal systems involved in the control of central nervous system-ghrelin action. We identified tachykinin-1 (Tac1) as a gene negatively regulated by ghrelin in the hypothalamus. Furthermore, we identified neuropeptide k as the TAC1-derived peptide with more prominent activity, inducing negative energy balance when delivered directly into the brain. Conversely, loss of Tac1 expression enhances the effectiveness of ghrelin promoting fat mass gain both in male and in female mice and increases the susceptibility to diet-induced obesity in ovariectomized mice. Taken together, our data demonstrate a role TAC1 in the control energy balance by regulating the levels of adiposity in response to ghrelin administration and to changes in the status of the gonadal function.

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