INTRODUCTION:

Corpulence is an important factor that precipitated and associated with other diseases such as diabetes, hypertension, and coronary artery disease that accompanied platelet aggregation¹. The association between corpulence and the occurrence of dyslipidemia, increased blood pressure and impaired glucose tolerance was termed as metabolic syndrome². In adipocyte, adipokines regulate adipocyte growth, maturation, and enlargement, in addition to adjust immune cell function inside the adipose tissue. While in outside of adipocyte, adipokines regulate many biological process in different organs such as muscles, liver, and brain³.

In normal size adipocyte, adipokines released in levels that maintain normal function of other tissues, whereas in corpulence at which the adipocyte enlarged, inflamed and released adipokines in manner that enhanced the incidence of diabetes, arteriosclerosis, inflammation and insulin resistance. Therefore, certain adipokines used as diagnostic tool for diabetes prediction and progression^4,5.

Interestingly, knowing the details of adipokine structure, behavior, its specific recipients, and functions are important for using this adipokine to treat its associated diseases with minimal adverse effects. This approach could occur by synthesis adipokine analog as therapeutic drug (adipokine agonist) or forming drug that inhibit particular adipokine (adipokine antagonist) and produce therapeutic effects. This review focused on many types of adipokines and presented their associations with corpulence or with other diseases or disorders.The most prominent types of adipokines are stated below.

LEPTIN:

Leptin is a protein released by adipose tissue and act both centrally in hypothalamus and peripherally in other tissues. It has many essential functions regarding dietary intake, energy utilization, metabolism of glucose, reproduction and others⁶. Centrally, Leptin can reduce the expression of orectic peptide (like neuropeptide Y) and increase the expression of anorectic peptides that lead to decrease dietary intake⁷. Many studies found that female leptin level was higher than male leptin level for the same age and body weight because of variation in body's fat content. Additionally serum leptin level was directly proportional to body mass index (BMI) in corpulent subjects and in hypothyroid patients^8,9.

The used of leptin as therapeutic drug involved recombinant leptin hormone which is used for the treatment of selected cases of congenital leptin deficiency in some center in united states and European but not available for usual clinical use¹⁰. Although leptin hormone has essential role in decreasing appetite and increasing energy utilization, but the use of leptin analog drug in the treatment of corpulence will not effect on decreasing body weight because corpulent patient already have high plasma level of leptin and have tissue resistance to leptin^11,12. Therefore the use of Metreleptin, leptin analog, for the treatment of corpulence is failed and is approved by FDA only for the treatment of lipodystrophy in patients with diabetes and/or hypertriglyceridemia¹³.

Interestingly, another study found that the addition of amylin to leptin analog can improve the leptin sensitivity therefore a new formula (pramlintide and metreleptin) was tested in corpulent patients for more than five months in clinical trial and verified that this combination can considerably decreases the body weight ¹⁴. Later on, this combination will not approve for the treatment of corpulence due to adverse effects that involved production of antibody and allergy.

CHEMERIN:

Chemerin, also called retinoic acid receptor responder protein 2, is a protein secreted by adipocyte and hepatocyte and bound to its receptor, chemokine-like receptor-1,that is presented vastly in adipose tissue and responsible for enhancing fat anabolism and adipocyte maturation. As well, chemerin has a role in inflammatory reaction by acting as attractive protein for other immune proteins¹⁵. Chemerin directly associated with risk factors of corpulence such as insulin resistance, hyperlipidemia, and hypertension. Therefore chemerin may act as a link between adipocyte and inflammatory reaction that associated with corpulence and hence chemerin may use as a biomarker for detection of insulin resistance in subjects with or without metabolic syndrome¹⁶.

ADIPONECTIN:

Adiponectin is a protein produced by adipocyte and has many functions related to increase the sensitivity of the tissue to insulin such as vascular tissues, decrease the inflammation, decrease the incidence of apoptosis phenomenon, and centrally adiponectin can enhance utilization of energy and hence decreasing weight¹⁷. The release of adiponectin from adipocyte depended on clinical condition of the body and its associated hormones or factors¹⁸.

Conspicuously, in metabolic syndrome that caused increase level of hormones such as cortisol, or insulin or of immune factors such as TNFα or IL-6, the level of adiponectin decreased and inversely correlated with these factors. While in acute coronary disease condition, the adiponectin level seem to be not related to this condition or its associated factors¹⁹.

Recombinant adiponectin produced and tested. However, the results of tests are controversial, some studies found that recombinant adiponectin can ameliorate liver sensitivity to insulin and can maintain body weight and blood glucose level²⁰. Contrary, other study contradicted these results and reported that this decline in the level of results may be due to the inadequacy in the formation of recombinant adiponectin²¹.

Adipo Ron, synthetic agonist to adiponectin receptor, orally administered and tested on mice. This product is specifically bound to the receptor of adiponectin and can improve the sensitivity of insulin and maintain blood glucose level²². Additional improvement needed in the synthesis of drug analog to adiponectin and examined its therapeutic effects and adverse effects on human.

NAMPT/ VISFATIN:

Nicotinamide phosphoribosyl transferase (NAMPT) also called visfatin is another type of adipocytokine released, and signified by guts fat cells. As well, many tissues such as adipose tissue can signify NAMPT/visfatin. The biological role of NAMPT/visfatin involved imitating insulin activity and thereby glucose haemostasis by linking to its specific location on the receptor of insulin. Other function of NAMPT/visfatin related to its role in signification of genes that control oxidative status, response to inflammation; enhance function of β cell, and withholding apoptosis of neutrophil²³. Additionally, NAMPT/visfatin has an essential enzymatic activity in producing of nicotinamide mononucleotide (NMN), which has a role in amending glucose level and enhancing the sensitivity of hepatocyte to insulin. Therefore the declined level of NAMPT/visfatin may enhance the possibility of type 2 diabetes especially in old age and high feeding states²⁴.

OMENTIN:

Omentin is an adipokine that not released by adipocyte but released by stromal cells of guts adipose tissue, which involves endothelial cells, macrophages, lymphocytes, preadipocytes. As well, other cells can produce omentin such as Paneth cells of intestine and named as intelectin²⁵. Omentin has a role in glucose haemostasis in a way analogous to that of adiponectin. Likewise, many studies found that the blood level of omentin-1 decreased in corpulent subjects and in patients with high blood level of glucose or with low insulin sensitivity as in diabetes. Therefore, the presence of omentin in normal level in blood may exert protective action against inflammation, diabetes, and atherogenesis thereafter decrease the need for antiplatelet drugs^16,26.

VASPIN:

Vaspin is an adipokine that inhibit serine protease, especially kallikrein 7, and released by visceral adipose tissue. It is name came from visceral adipose tissue-derived serpin (serpin A12), but it is also present in skin, hypothalamus, pancreatic islets, and stomach²⁷. Many study found that vaspin has an effect on insulin sensitivity and its level elevated in obese patients with abnormal sensitivity to the insulin²⁸. Other stated conflicting results that elevated vaspin level modulate the sensitivity of insulin²⁹.

DIPEPTIDYL PEPTIDASE-4 (DPP-4):

Dipeptidyl peptidase-4 (DPP-4) is an adipokine with enzymatic properteies, hydrolytic type, that lead to deactivation of hormones called incretins which include glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). Incretins hormones produced by mucosa of intestine and have a role in increasing insulin secretion after meal especially glucose meal and thereafter decreasing glucagon hormone release³⁰. Additionally, DPP-4 may directly enhance the resistance of insulin in myocytes and adipocytes³¹. Studies documented that in patients with type 2 diabetes incretin hormones were low and DPP4 was elevated than normal. As well, the level of DPP4 was raised in obese subjects as matched to lean one³².

The deactivation of DPP4 leads to decrease the rate of catabolism of incretin hormone and thereafter elongate the survival of these hormones and increase insulin secretion. So, this feature encourage the synthesis of drugs under new class of antidiabetes drugs. Saxagliptin is one of anti DPP4 drugs that used for treatment of diabetes, and many researchers found that it has a capability to decrease the elevated blood level of leptin and visfatin and increase the reducing blood level of adiponectin³².

CONCLUSION:

Adipokines are associated either directly or indirectly with the balance of food intake and energy burning and thereafter with the body weight. The existence of unbalance state for long period may precipitate diseases such as metabolic disease or inflammatory disease that often associated with the pathologic corpulence. The treatment of weight gain in these conditions may need to normalize the blood level of these adipokines, which can occur either directly or indirectly. Therefore, we need to understand the behaviors of these adipokines on many biological processes and assess their responses to many drugs that used for the treatment of metabolic or inflammatory diseases.

CONFLICT OF INTEREST:

There is no conflict of interest to declare.

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Received on 31.08.2021 Modified on 04.02.2022

Research J. Pharm. and Tech 2022; 15(9):4315-4318.

DOI: 10.52711/0974-360X.2022.00724