Objective: The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p < 0.05 was considered significant.
Results: There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC.
Conclusion: In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.
OBJECTIVE: The study aimed to investigate the effect of African walnuts (Tetracarpidium conophorum) on lipids storage and the regulatory enzymes of hepatic lipid metabolism in obese rats.
METHODS: Nuts were extracted in ethanol (WE) and further separated to obtain the ethyl-acetate fraction (ET) and the residue (RES). These were administered orally to 3 groups of monosodium glutamate- obese rats (n = 6), respectively, for 6 weeks. Other groups in the study were: normal (NC), obese control (OC) and standard control (SC) which received orlistat. Hepatic total lipids, total phospholipids, triacylglycerol (TG), total cholesterol (TCHOL), 3-hydroxyl-3-methylglutaryl-CoA (HMG-CoA) reductase and paraoxonase were studied.
RESULTS: Total lipids, TG and TCHOL which increased in OC compared to NC group, decreased. HMG-CoA reductase activity decreased in the 3 study groups relative to OC. Paraoxonase activity which decreased in OC was up-regulated, while the magnitude of hepatic cholesterol decreased from 94.32 % in OC to 52.19, 65.43 and 47.04 % with WE, ET and RES, respectively. Flavonoids, alkaloids, glycosides, tannins and saponins were detected in the nut. GC-MS analysis revealed 16, 18 and 10 volatile components in WE, ET and RES, respectively. Unsaturated fatty acids (linolenic acids: 33.33, 47.95 and 50.93 %, and α-linolenic acids: 25, 19.66 and 26.63 %) in WE, ET and RES, respectively, are the most abundant, and likely to be responsible for the observed activity.
CONCLUSION: African walnuts can prevent hepatic lipid accumulation through reciprocal actions on HMG-CoA reductase and paraoxonase in obesity.
MATERIALS AND METHODS: Whole ethanol extract (WE) of the nuts, and its liquid-liquid fractions-ethyl acetate (ET) and residue (RES) were separately administered to obese rats for 6 weeks. The normal (NC) and obese (OC) controls received normal saline and the standard control (SC), orlistat (5.14 mg/kg b.w.), during the same period. Thereafter, the animals were euthanized and the adipose, brain, kidneys and heart tissues were studied.
RESULTS: The change in body weight to naso-anal length which increased by 63.52 % in OC compared to NC (p < 0.05), decreased by 57.88, 85.80 and 70.20 % in WE, ET and RES-treated groups, respectively, relative to the OC (p < 0.05). Also, adipose tissue weights were lowered upon treatment with the extracts and fractions versus OC (p < 0.05). Total lipids, phospholipids, triacylglycerol and cholesterol concentrations in the studied tissues which were higher in OC (p < 0.05) were lowered (p < 0.05) and compared favorably with SC. Further, malondialdehyde levels in the tissues were lowered upon treatment, compared to the OC (p < 0.05). Glutathione level and activities of glutathione peroxidase, superoxide dismutase and glutathione-S-transferase which were decreased (p < 0.05) in OC, were restored upon treatment with the extracts, relative to the obese control (p < 0.05).
SIGNIFICANCE: African walnuts assuaged lipogenesis, oxidative stress and peroxidation in extra-hepatic tissues of obese rats, hence, may attenuate ectopic fat accumulation and its associated pathogenesis.
METHODS: The study involved 235 Malaysian subjects who were randomly selected (66 normal weight subjects, 97 overweight, 59 obese subjects, and 13 subjects who were underweight). Serum sDPP4 and active GLP-1 levels were examined by enzyme-linked immunosorbent assay (ELISA). Also, body mass index kg/m(2) (BMI), lipid profiles, insulin and glucose levels were evaluated. Insulin resistance (IR) was estimated via the homeostasis model assessment for insulin resistance (HOMA-IR).
RESULTS: Serum sDPP4 levels were significantly higher in obese subjects compared to normal weight subjects (p=0.034), whereas serum levels of active GLP-1 were lower (p=0.021). In obese subjects, sDPP4 levels correlated negatively with active GLP-1 levels (r(2)=-0.326, p=0.015). Furthermore, linear regression showed that sDPP4 levels were positively associated with insulin resistance (B=82.28, p=0.023) in obese subjects.
CONCLUSION: Elevated serum sDPP4 levels and reduced GLP-1 levels were observed in obese subjects. In addition, sDPP4 levels correlated negatively with active GLP-1 levels but was positively associated with insulin resistance. This finding provides evidence that sDPP4 and GLP-1 may play an important role in the pathogenesis of obesity, suggesting that sDPP4 may be valuable as an early marker for the augmented risk of obesity and insulin resistance.
PATIENTS AND METHODS: Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy.
RESULTS: Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01).
CONCLUSIONS: Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.
AIM OF THE STUDY: This study aims to investigate the anti-obesity and lipid lowering effects of ethanolic extract of C. cauliflora leaves and its major compound (vitexin) in C57BL/6 obese mice induced by high-fat diet (HFD), as well as to further identify the molecular mechanism underlying this action.
METHODS AND MATERIAL: Male C57BL/6 mice were fed with HFD (60% fat) for 16 weeks to become obese. The treatment started during the last 8 weeks of HFD feeding and the obese mice were treated with C. cauliflora leaf extract at 200 and 400 mg/kg/day, orlistat (10 mg/kg) and vitexin (10 mg/kg).
RESULTS: The oral administration of C. cauliflora (400 and 200 mg/kg) and vitexin significantly reduced body weight, adipose tissue and liver weight and lipid accumulation in the liver compared to control HFD group. Both doses of C. cauliflora also significantly (P ≤ 0.05) decreased serum triglyceride, LDL, lipase, IL-6, peptide YY, resistin levels, hyperglycemia, hyperinsulinemia, and hyperleptinemia compared to the control HFD group. Moreover, C. cauliflora significantly up-regulated the expression of adiponectin, Glut4, Mtor, IRS-1 and InsR genes, and significantly decreased the expression of Lepr in white adipose tissue. Furthermore, C. cauliflora significantly up-regulated the expression of hypothalamus Glut4, Mtor and NF-kB genes. GC-MS analysis of C. cauliflora leaves detected the presence of phytol, vitamin E and β-sitosterol. Besides, the phytochemical evaluation of C. cauliflora leaves showed the presence of flavonoid, saponin and phenolic compounds.
CONCLUSION: This study shows interesting outcomes of C. cauliflora against HFD-induced obesity and associated metabolic abnormalities. Therefore, the C. cauliflora extract could be a potentially effective agent for obesity management and its related metabolic disorders such as insulin resistance and hyperlipidemia.