Published online Jan 15, 2018. doi: 10.4239/wjd.v9.i1.25
Peer-review started: February 12, 2017
First decision: May 17, 2017
Revised: November 17, 2017
Accepted: December 4, 2017
Article in press: December 4, 2017
Published online: January 15, 2018
Obestatin is a gut hormone, derived from the same gene as ghrelin and involved in food intake regulation. This peptide, initially proposed to bind to the G protein-coupled receptor GPR39 is active in the digestive tract, pituitary and adipose tissues. Initially, obestatin was reported to inhibit triacylglycerol hydrolysis in cultured murine 3T3-L1 adipocytes and in human adipocytes. Another insulin-like property was added to the panel of obestatin actions: The stimulation of glucose transport into fat cells. However, several recent reports have indicated that obestatin may activate lipolysis and raised confusion about its role in the modulation of triacylglycerol storage/mobilization. Thus, it was of interest to verify whether processes that are exquisitely regulated by insulin (glucose utilisation and lipid mobilisation by adipocytes) were also modulated by obestatin in human adipocytes.
The study aimed at determining complete dose-dependent effects of human obestatin in human subcutaneous fat cells. Such approach brings additional evidence that obestatin cannot readily and rapidly reproduce the antilipolytic action of insulin, while it confirms that the α2-adrenergic agonist bromoxidine surpasses the insulin-induced inhibition of lipolysis in human fat cells. At 1 μmol/L, obestatin induces a moderate activation of hexose uptake in fat cells, the magnitude of which is too modest to assess definitively that the peptide acts as an insulin mimicker.
Although a direct regulatory action on adipocyte lipolysis/lipogenesis does not seem to contribute to the multifunctional in vivo actions of obestatin, our observations do not exclude a long-term influence of the peptide on adipocyte biology in healthy, obese or diabetic subjects. Whether such long-term actions might be beneficial to combat obesity and diabetes linked complications remains to be clarified.
Obestatin is primarily a gut hormone, derived from the same gene as ghrelin and should belong to the multiple steps linking digestive tract function and food intake regulation. Nevertheless, its apparent lack of direct action on target cells such as the adipocytes, which are involved in the regulation of energy balance and glucose handling, does not allow proposing novel obestatin-based therapeutic approaches in combating obesity and diabetes.
ANP: Atrial natriuretic peptide; SCAT: Subcutaneous adipose tissue; BMI: Body mass index SEM: Standard error of the mean; 2-DG: 2-deoxyglucose.