Abstract
ABSTRACT We recently identified acyl coenzyme A-binding protein (ACBP)/diazepam binding inhibitor (DBI) as a novel ‘hunger factor’: a protein that is upregulated in human or murine obesity and that, if administered to mice, causes hyperphagy, adipogenesis and obesity. Conversely, neutralization of ACBP/DBI by systemic injection of neutralizing monoclonal antibodies or autoantibodies produced after auto-immunization against ACBP/DBI has anorexigenic and lipolytic effects. Thus, neutralization of ACBP/DBI results in reduced food intake subsequent to the activation of anorexigenic neurons and the inactivation of orexigenic neurons in the hypothalamus. Moreover, ACBP/DBI neutralization results into enhanced triglyceride lipolysis in white fat, a surge in free fatty acids in the plasma, enhanced incorporation of glycerol-derived carbon atoms into glucose, as well as an increase in β-oxidation, resulting in a net reduction of fat mass. Importantly, ACBP/DBI neutralization also stimulated an increase in autophagy in various organs, suggesting that it might mediate anti-ageing effects.
Highlights
Obesity is the most prevalent pathological condition worldwide
It is well established that induction of autophagy by caloric restriction (CR) or so-called CR mimetics (CRMs) has a positive impact on health span and lifespan [3,5,6], suggesting that the obesity-related suppression of autophagy might, on the contrary, have negative effects on organismal health and longevity
We found that various human and mouse cell types release acyl coenzyme A-binding protein (ACBP)/diazepam binding inhibitor (DBI) upon induction of autophagy into the extracellular space
Summary
Obesity is the most prevalent pathological condition worldwide. epidemiological factors such as exaggerated carbohydrate intake and sedentary life style could constitute a basis for obesity prevention, the actual prevalence of obesity (40% of the adult US population) [1] calls for novel therapeutic interventions. A 24-hour fasting period caused an elevation of circulating ACBP/ DBI levels in the plasma of mice [8–10]. We subsequently discovered that intraperitoneal or intravenous injection of recombinant ACBP/DBI protein into mice was sufficient to induce an immediate (within less than 30 min) hyperphagic response with activation of orexigenic neurons and the inhibition of anorexigenic centres in the hypothalamus [8]. In conditions of a glucose clamp, the hyperphagic response induced by ACBP/DBI injection is lost, and the activation of orexigenic neurons is suppressed [8].
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