Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

Abstract

feature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R concentration, which suggests higher resistance of peripheral tissues towards the action of leptin. INTRODUCTIONLeptin -the ob gene product -is a circulating 16-kDa peptide hormone secreted mainly by adipocytes of white fat tissue. It regulates food intake, body fat, insulin action, thermogenesis, induction of angiogenesis, and modulation of the immune system. Leptin synthesis in adipocytes is regulated by several hormones [1] . Leptin action in peripheral tissues involves interaction with specific transmembrane receptors. The leptin receptor (Ob-R), which is a member of the class-1 cytokine receptor family, may be an important determinant of leptin sensitivity. Ob-R was originally demonstrated in hypothalamic neurons, through which leptin regulates food intake and body weight [2] . Alongside several membrane-bound isoforms of Ob-R, with varying cytoplasmic length and with the same extracellular domain, a soluble form of the leptin receptor (sOb-R) can be demonstrated. sOb-R represents the main leptin-binding compound in plasma, which results in fractions of bound and free leptin in plasma [3] . The balance between the free form, the rapidly bioavailable compartment, and bound leptin regulates leptin bioavailability [4] . However, the precise pathophysiological role of sOb-R has not yet been defined.Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a common and potentially severe condition often associated with obesity, type 2 diabetes and Abstract AIM:To determine the role of leptin system in non-alcoholic fatty liver disease (NAFLD) development by delineating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). METHODS:Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radioimmunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected. RESULTS:Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the controls (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). There was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multivariate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently related to serum leptin levels. CONCLUSION:Elevated serum leptin seems to be a

Serum levels of leptin receptor in patients with malignant melanoma as a new tumor marker

“…In the setting of obesity, the body becomes resistant to the effects of leptin, resulting in paradoxical weight gain in the setting of high levels of circulating leptin (10). It has been shown that there is strong negative correlation between serum levels of leptin and leptin receptor in patients with non-alcoholic fatty liver disease (11). These findings point out to insulin resistance as a potentially independent risk factor for melanoma (12).…”

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

“…Conversely, the circulating levels of adiponectin are inversely proportional to body fat content and become reduced in patients with NAFLD. [38][39][40][41] Oxidative stress and mitochondrial dysfunction play a wellreported role in NASH, with a direct correlation between the degrees of oxidative stress and the severity of liver disease. Structural mitochondrial abnormalities and impairment of mitochondrial respiratory chain activity have been reported in human studies.…”

Leptin and leptin receptor polymorphisms are related to body mass index in a Turkish population

“…Leptin receptor is a member of the class-1 cytokine receptor family and it is an important determinant of leptin sensitivity originally found in hypothalamic neurons. However, alongside the membrane-bound forms of this receptor, there is also a soluble form in plasma (1). The function of this soluble form is not known yet, but it is thought to contribute to the delay in clearance of leptin (3).…”

“…An inverse relationship was found between leptin and soluble leptin receptor levels (4). The balance between bound and free leptin depends on the plasma concentration of this soluble leptin receptor (1,5). The ratio between total and soluble leptin concentration was used as the free leptin index, indicating leptin resistance (5).…”

“…Leptin is an essential hormone related to weight gain and obesity, controlling energy balance and metabolism in the human body. It is a peptide hormone, secreted from white adipose tissue as a signal to the brain, and has a primary influence on body weight by coordinating the metabolic, endocrine, and behavioral responses to starvation (1). Insensitivity of the leptin receptor is known as leptin resistance.…”