Fat accumulation has been shown to play important roles in the development of obesity-related disorders such as atherosclerosis, diabetes mellitus and hypertension. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine functions. These are achieved predominantly through release of adipocytokines, which include several novel molecules released by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells, like TNF-alpha and IL-6. Adipocytokines may affect cardiovascular, hepatic, muscular and metabolic function. In this review, the recent research work of adipocytokines will be discussed.
Adipokines ; physiology ; Adiponectin ; physiology ; Adipose Tissue ; chemistry ; physiology ; Humans ; Leptin ; physiology ; Resistin ; physiology

Animals ; Humans ; Inflammation ; etiology ; Intercellular Signaling Peptides and Proteins ; physiology ; Nerve Growth Factor ; physiology ; Proteins ; physiology ; Resistin ; physiology

Adiponectin ; Ghrelin ; physiology ; Growth Hormone-Releasing Hormone ; Humans ; Leptin ; Receptors, Ghrelin ; Resistin

For the regulation of energy balance in various internal organs including gut, pancreas and liver, visceral adipose tissue and brain perform important sensing and signaling roles via neural and endocrine pathway. Among these, adipose tissue has been known as a simple energy-storing organ, which stores excess energy in triglyceride. However, it became apparent that adipocytes have various receptors related to energy homeostasis, and secrete adipocytokines by endocrine, paracrine and autocrine mechanisms. In this review, basic roles of adipocytes in energy homeostasis and the correlation between adipocyte signals and digestive diseases are discussed.
Adipocytes/*metabolism ; Adipokines/*physiology ; Adiponectin/physiology ; Digestive System Diseases/*metabolism ; *Energy Metabolism ; Homeostasis ; Humans ; Leptin/physiology ; Peroxisome Proliferator-Activated Receptors/physiology ; Resistin/physiology ; Signal Transduction

Adipose tissue is not simply a depot of energy, but is an active endocrine organ. The adipokines play an important role in the pathogenesis of metabolic syndrome. The proinflammatory adipokines secreted from expanded visceral adipose tissue directly induce insulin resistance and vascular injuries. A better understanding of the endocrine function of adipose tissue may lead to more rational therapy for metabolic syndrome.
Adiponectin ; physiology ; Adipose Tissue ; physiopathology ; Drug Design ; Leptin ; physiology ; Metabolic Syndrome ; drug therapy ; physiopathology ; Resistin ; physiology ; Tumor Necrosis Factor-alpha ; physiology

Resistin, a newly discovered peptide hormone mainly secreted by adipose tissues, is present at high levels in serum of obese mice and may be a potential link between obesity and insulin resistance in rodents. However, some studies of rat and mouse models have associated insulin resistance and obesity with decreased resistin expression. In humans, no relationship between resistin level and insulin resistance or adiposity was observed. This suggests that additional studies are necessary to determine the specific role of resistin in the regulation of energy metabolism and adipogenesis. In the present study, we investigated the effect of resistin in vivo on glucose and lipid metabolism by over-expressing resistin in mice by intramuscular injection of a recombinant eukaryotic expression vector pcDNA3.1-Retn encoding porcine resistin gene. After injection, serum resistin and serum glucose (GLU) levels were significantly increased in the pcDNA3.1-Retn-treated mice; there was an obvious difference in total cholesterol (TC) level between the experiment and the control groups on Day 30. In pcDNA3.1-Retn-treated mice, both free fatty acid (FFA) and high density lipoprotein (HDL) cholesterol levels were markedly lower than those of control, whereas HDL cholesterol and triglyceride (TG) levels did not differ between the two groups. Furthermore, lipase activity was expressly lower on Day 20. Our data suggest that resistin over-expressed in mice might be responsible for insulin resistance and parameters related to glucose and lipid metabolism were changed accordingly.
Animals ; Blood Glucose ; analysis ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Fatty Acids, Nonesterified ; blood ; Glucose ; metabolism ; HeLa Cells ; Humans ; Lipid Metabolism ; Male ; Mice ; Resistin ; blood ; physiology ; Triglycerides ; blood

OBJECTIVEResistin was thought to link the obesity to type 2 diabetes. This study aimed to investigate the effect of resistin on insulinoma cell proliferation.

METHODSpcDNA3.1-resistin was transfected into rat insulinoma cells RINm5F. Cell proliferation was assessed by the MTT assay. The resistin and SOCS3 mRNA levels were assessed by RT-PCR. The total Akt level and the phosphorylation status were assessed by Western blot.

RESULTSThe over-expressed resistin inhibited the RINm5F cell proliferation (p<0.05). SOCS-3 expression was up-regulated by resistin over-expression (3.2 folds over the control; p<0.05). Akt phosphorylation was down-regulated by resistin over-expression (0.6 fold over the control; p<0.05).

CONCLUSIONSResistin impairs the rat insulinoma cell RINm5F proliferation. This might be attributed to a down-regulation of Akt level caused by increased SOCS-3 expression.

Animals ; Cell Line, Tumor ; Cell Proliferation ; Insulinoma ; pathology ; Pancreatic Neoplasms ; pathology ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Resistin ; genetics ; physiology ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; genetics ; Transfection

OBJECTIVETo study the effect of a new obesity-related gene NYGGF4 on the insulin sensitivity and secretory function of adipocytes.

METHODS3T3-L1 preadipocytes transfected with either an empty expression vector (pcDNA3.1; control group) or an NYGGF4 expression vector (NYGGF4-pcDNA3.1) were cultured in vitro and differentiated into the matured adipocytes with the standard insulin plus dexamethasone plus 3-isobutyl-methylxanthine (MDI) induction cocktail. 2-deoxy-D-[3H] glucose uptake was determined by liquid scintillation counting. Western blot was performed to detect the protein content and translocation of glucose transporter 4 (GLUT4). The supernatant concentrations of TNF-alpha, IL-6, adiponectin and resistin were measured using ELISA.

RESULTSNYGGF4 over-expression in 3T3-L1 adipocytes reduced insulin-stimulated glucose uptake. NYGGF4 over-expression impaired insulin-stimulated GLUT4 translocation without affecting the total protein content of GLUT4. The concentrations of TNF-alpha, IL-6, adiponectin and resistin in the culture medium of 3T3-L1 transfected with NYGGF4 were not significantly different from those in the control group.

CONCLUSIONSNYGGF4 over-expression impairs the insulin sensitivity of 3T3-L1 adipocytes through decreasing GLUT4 translocation and had no effects on the secretory function of adipocytes.

3T3-L1 Cells ; Adipocytes ; drug effects ; secretion ; Adiponectin ; secretion ; Animals ; Carrier Proteins ; genetics ; physiology ; Glucose ; metabolism ; Glucose Transporter Type 4 ; analysis ; metabolism ; Insulin ; pharmacology ; Interleukin-6 ; secretion ; Mice ; Resistin ; analysis ; Transfection ; Tumor Necrosis Factor-alpha ; secretion

BACKGROUNDHyperinsulinemic euglycemic clamp is the gold standard to evaluate the insulin sensitivity, but it is too complicated and expensive to use in clinic. We tried to find an alternative indicator to reflect insulin sensitivity. To evaluate the association between the four adipokines, adiponectin, leptin, resistin and tumor necrosis factor-alpha (TNF-alpha) with insulin sensitivity, we used a hyperinsulinemic euglycemic clamp to test insulin sensitivity in Chinese patients with obesity and type 1 or type 2 diabetes mellitus versus controls.

METHODSIn this parallel control study, we tested insulin sensitivity using a hyperinsulinemic euglycemic clamp in different groups, then examined levels of adiponectin, leptin, resistin and TNF-alpha in serum, and the relationship between the different adipokines and glucose disposal rate (M value), as well as insulin sensitivity index (M value/insulin, M/I), which are the "gold standard" indices of insulin sensitivity.

RESULTSThere were significant differences in mean leptin values in the four adipokines from the four different groups (P < 0.001; comparison of the variation between different groups was analyzed by variance analysis). Compared to controls (using multiple comparison two-way Dunnett t test), only the leptin level showed significant differences in the four adipokines from the four different groups at the same time (P < 0.001). The association analysis between the different adipokines and M or M/I values also showed that only leptin negatively correlated with M (r = -0.64, P < 0.001) or M/I values (r = -0.56, P < 0.001); there was no relationship between the other three adipokines and M or M/I values.

CONCLUSIONOnly leptin was associated with M or M/I values. Therefore, leptin might be one of the predictive factors of the degree of insulin resistance and risk of the accompanying disease.

Adipokines ; blood ; Adiponectin ; blood ; Asian Continental Ancestry Group ; Diabetes Mellitus, Type 1 ; blood ; Diabetes Mellitus, Type 2 ; blood ; Glucose Clamp Technique ; Humans ; Insulin Resistance ; physiology ; Leptin ; blood ; Obesity ; blood ; Resistin ; blood ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo analyze the role of resistin in insulin resistance (IR) through investigating the variation of plasma resistin levels and single-nucleotide polymorphisms (SNPs) in resistin gene 5' flanking region in stroke patients.

METHODSIn 103 atherothrombotic cerebral infarction (ACI) patients, 85 lacunar infarction (LI) patients, 70 intracerebral hemorrhage (ICH) patients, and 86 healthy controls, plasma resistin and insulin levels were measured by ELISA, SNPs in resistin gene 5' flanking region were detected by PCR and direct DNA sequencing. The subjects' body height and weight, the body mass index, quantitative insulin sensitivity check index (QUICKI), blood pressure, and the concentration of fasting plasma glucose, triglyceride, total cholesterol, creatinine, low-density lipoprotein, and high-density lipoprotein were also determined.

RESULTSQUICKI was significantly lower in the ACI and ICH patients (0.316 +/- 0.037 and 0.309 +/- 0.032, respectively) than that in the controls (0.342 +/- 0.043, P < 0.001), while plasma resistin level was significantly higher in the ACI and ICH patients (6.36 +/- 3.79 and 7.15 +/- 4.27 ng/mL, respectively) than that in the controls (5.28 +/- 2.56 ng/mL, P < 0.05), but such difference was not observed in the LI patients compared with controls. There was a statistically negative correlation between plasma resistin level with QUICKI (r = -0.228, P < 0.001). The distributions of allele and genotype frequencies of resistin gene - 420C > G and - 537A > C SNPs were not significantly different among the different groups, and those SNPs were not correlated with other clinical and biochemical parameters.

CONCLUSIONSPlasma resistin is associated with stroke by participating in the development of IR. The SNPs in resistin gene 5' flanking region has no impact on the plasma resistin level.

Adult ; Aged ; Aged, 80 and over ; Blood Glucose ; metabolism ; Cerebral Infarction ; blood ; genetics ; Creatinine ; blood ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; physiology ; Intracranial Arteriosclerosis ; blood ; genetics ; Lipoproteins ; blood ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Resistin ; blood ; genetics ; Stroke ; blood ; genetics ; Triglycerides ; blood