Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SIRT1 is a nicotinamide adenosine dinucleotide-dependent deacetylase that orchestrates key metabolic adaptations to nutrient deprivation in peripheral tissues. SIRT1 is induced also in the brain by reduced energy intake. However, very little is known about SIRT1 distribution and the biochemical phenotypes of SIRT1-expressing cells in the neuraxis. Unknown are also the brain sites in which SIRT1 is regulated by energy availability and whether these regulations are altered in a genetic model of obesity. To address these issues, we performed in situ hybridization histochemistry analyses and found that Sirt1 mRNA is highly expressed in metabolically relevant sites. These include, but are not limited to, the hypothalamic arcuate, ventromedial, dorsomedial, and paraventricular nuclei and the area postrema and the nucleus of the solitary tract in the hindbrain. Of note, our single-cell reverse transcription-PCR analyses revealed that Sirt1 mRNA is expressed in pro-opiomelanocortin neurons that are critical for normal body weight and glucose homeostasis. We also found that SIRT1 protein levels are restrictedly increased in the hypothalamus in the fasted brain. Of note, we found that this hypothalamic-specific, fasting-induced SIRT1 regulation is altered in leptin-deficient, obese mice. Collectively, our findings establish the distribution of Sirt1 mRNA throughout the neuraxis and suggest a previously unrecognized role of brain SIRT1 in regulating energy homeostasis.
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PMID:Brain SIRT1: anatomical distribution and regulation by energy availability. 1882 56

Individuals who live in industrialized countries often eat a calorie-rich diet and perform little physical activity. These habits are thought to be critical contributors to the rapidly rising incidence of obesity, a condition that affects hundreds of millions of people worldwide. High-calorie intake alters metabolic-sensing pathways in central nervous system neurons, and these changes have pathogenic roles in the development of obesity. This review aims to summarize our current knowledge about the neuronal populations (the central melanocortin system in particular) and transcriptional regulators, including STAT3 and FOXO1, that are involved in the maintenance of normal body weight. We describe the interactions between these transcriptional factors and their target genes, which encode the main appetite-regulating neuropeptides (agouti-related peptide and alpha-melanocyte-stimulating hormone). We discuss the transcriptional co-activator PGC-1-alpha and the supposed metabolic-sensor protein SIRT1, and their potential roles as targets for novel antiobesity medications.
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PMID:The role of transcriptional regulators in central control of appetite and body weight. 1922 36

Feeding on high-calorie (HC) diets induces serious metabolic imbalances, including obesity. Understanding the mechanisms against excessive body weight gain is critical for developing effective antiobesity strategies. Here we show that lack of nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase SIRT1 in pro-opiomelanocortin (POMC) neurons causes hypersensitivity to diet-induced obesity due to reduced energy expenditure. The ability of leptin to properly engage the phosphoinositide 3-kinase (PI3K) signaling in POMC neurons and elicit remodeling of perigonadal white adipose tissue (WAT) is severely compromised in mutant mice. Also, electrophysiological and histomorphomolecular analyses indicate a selective reduction in sympathetic nerve activity and brown-fat-like characteristics in perigonadal WAT of mutant mice, suggesting a physiologically important role for POMC neurons in controlling this visceral fat depot. In summary, our results provide direct genetic evidence that SIRT1 in POMC neurons is required for normal autonomic adaptations against diet-induced obesity.
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PMID:SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity. 2062 Sep 97

Aging is characterized by a progressive loss of several physiological functions that can cause various age-related disorders. Several factors have been identified as causes of aging to elucidate the decline in functions. Various aspects of physiological deterioration are controlled by the hypothalamus, a critical brain region that connects the neuroendocrine system to physiological functions. In addition, functional alterations in a set of agouti-related peptide/neuropeptide Y (AgRP/NPY) and pro-opiomelanocortin (POMC) neurons, a set of growth hormone-releasing hormone (GHRH) and somatostatin (SST) neurons, a set of arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) neurons, and a set of gonadotropin-releasing hormone (GnRH) and kisspeptin/neurokinin B/dynorphin (KNDy) neurons contribute to age-related physiological decline in energy metabolism, hormone regulation, circadian rhythm, and reproduction, respectively. The underlying cellular mechanism for the hypothalamus-mediated aging progression comprises dysregulation of nutrient sensing, altered intercellular communication, stem cell exhaustion, loss of proteostasis, and epigenetic alterations. Furthermore, mammalian target of rapamycin (mTOR), NF-kB, hypothalamic stem cell, autophagy, and SIRT1 have been recognized as critical factors or pathways mediating the mechanism. Perhaps, further dissection of these pathways or components could provide the potential for developing a therapeutic intervention for age-related diseases or the extension of healthy lifespan.
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PMID:Role of hypothalamus in aging and its underlying cellular mechanisms. 2972 30