Acyl ghrelin, desacyl ghrelin and their ratio affect hepatic steatosis via PPARγ signaling pathway

Ghrelin is an appetite hormone containing 28 amino acids [1], [2], [3]. This hormone is secreted by several tissues such as the stomach, brain, kidney, pancreas, liver, adipose tissue, and pituitary [4], [5]. The ghrelin hormone has 4 different forms in the body produced by the same ghrelin precursor [nonacylated (desacyl ghrelin), octanoylated (acyl ghrelin), decenoylated and decanoylated]. Acyl and desacyl ghrelin are the forms available in the plasma at the highest level. The desacyl ghrelin is thought to be produced as a result of the des-acylation of acyl ghrelin [6], [7].

It is known and available in the literature that ghrelin forms have different physiological functions in the body [8]. Although desacyl ghrelin was considered inactive in the early days, it is now known to have significant endocrine activity in the body [7]. While acyl ghrelin has a characteristic to increase appetite, growth hormone release, body weight, and insulin resistance, it is indicated that desacyl ghrelin plays a role in decreasing appetite and body weight and increasing insulin sensitivity [4], [9].

Non-alcoholic fatty liver disease (NAFLD) is a common public health issue both in developed and developing countries, and it is characterized by a broad liver damage spectrum ranging from simple steatosis to non-alcoholic steatohepatitis. In non-alcoholic fatty liver disease, an increase in de novo synthesis of fatty acids and triglyceride (TG) accumulation in hepatocytes occur [10]. Acyl-CoA, lysophosphatidic acid, diacylglycerol (DAG) lipid metabolites participate in the synthesis of TG in hepatocytes. Diacylglycerol plays an active role in the TG synthesis by regulating protein kinase C (PKC) activation. Therefore, excessive production of DAG leads to the development of NAFLD even in the absence of obesity [10], [11].

It is quite important to review acyl and desacyl ghrelins and the ratio of them to each other when investigating the underlying mechanism of hepatic lipogenesis and insulin resistance in NAFLD. In the literature, there are comprehensive studies that examined the effects of acyl ghrelin on appetite and hepatic steatosis; however, no comprehensive study is available on desacyl ghrelin. It is also understood from the recent research that the effects of the ratio of these two hormones to each other on hepatic steatosis, insulin resistance, and biochemical findings are rather important than the amount of acyl and ghrelin. Yet, no data was found in the literature regarding the effective ratios of acyl and desacyl ghrelin. This study was conducted to review the effects of acyl and desacyl forms of ghrelin hormone and the administration of these forms to rats in different doses on hepatic steatosis, insulin resistance, and biochemical parameters.

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