Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were elevated in obese patients and reduced in anorexia nervosa. In mice, systemic injection of ACBP protein inhibited autophagy, induced lipogenesis, reduced glycemia, and stimulated appetite as well as weight gain. We designed three approaches to neutralize ACBP, namely, inducible whole-body knockout, systemic administration of neutralizing antibodies, and induction of antiACBP autoantibodies in mice. ACBP neutralization enhanced autophagy, stimulated fatty acid oxidation, inhibited appetite, reduced weight gain in the context of a high-fat diet or leptin deficiency, and accelerated weight loss in response to dietary changes. In conclusion, neutralization of ACBP might constitute a strategy for treating obesity and its co-morbidities.
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PMID:Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity. 3180 Oct 56

DBI/ACBP (diazepam binding protein, acyl-CoA binding protein) participates in the regulation of fatty acid metabolism when it is localized within cells, whereas outside of cells it acts as a diazepam-binding protein. Recent results indicate that many different mammalian cell types release DBI/ACBP upon in vitro or in vivo starvation in a macroautophagy/autophagy-dependent fashion. The autophagy-associated release of DBI/ACBP elicits feedback inhibition of autophagy through 3 independent mechanisms. First, the depletion of DBI/ACBP from cells limits autophagy in a cell-autonomous fashion. Second, extracellular DBI/ACBP acts in a paracrine fashion to inhibit autophagy. Third, DBI/ACBP increasing in the systemic circulation acts as an activator of lipo-anabolism and feeding behavior, thus removing the cause of autophagy induction (starvation) and suppressing the phenomenon. DBI/ACBP expression is upregulated at the mRNA and protein levels in obese mice and humans, and its extracellular neutralization by antibodies controls food intake and increases lipo-catabolism. Current data support the contention that DBI/ACBP is an important pro-obesity factor. Abbreviations: DBI: diazepam binding protein, acyl-CoA binding protein; GABR: gamma-aminobutyric acid type A receptor; TSPO: translocator protein.
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PMID:Cell-autonomous, paracrine and neuroendocrine feedback regulation of autophagy by DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein): the obesity factor. 3142 3

Type-2 diabetes is characterized by glycosuria, hyperglycemia, glucose intolerance, hyperinsulinemia, and insulin resistance. One or several among these alterations are also found after starvation, ketogenic diet, and pharmacological treatment with rapamycin or antibody-mediated neutralization of the obesogenic factor ACBP/DBI. Thus, a variety of metabolic interventions that improve metabolic health can induce a transient state of "pseudo-diabetes".
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PMID:Pseudodiabetes-not a contraindication for metabolic interventions. 3160 89