Comprehensive proteomics and functional annotation of mouse brown adipose tissue.

Knowledge about the mouse brown adipose tissue (BAT) proteome can provide a deeper understanding of the function of mammalian BAT. Herein, a comprehensive analysis of interscapular BAT from C57BL/6J female mice was conducted by 2DLC and high-resolution mass spectrometry to construct a comprehensive proteome dataset of mouse BAT proteins. A total of 4949 nonredundant proteins were identified, and 4495 were quantified using the iBAQ method. According to the iBAQ values, the BAT proteome was divided into high-, middle- and low-abundance proteins. The functions of the high-abundance proteins were mainly related to glucose and fatty acid oxidation to produce heat for thermoregulation, while the functions of the middle- and low-abundance proteins were mainly related to protein synthesis and apoptosis, respectively. Additionally, 497 proteins were predicted to have signal peptides using SignalP4 software, and 75 were confirmed in previous studies. This study, for the first time, comprehensively profiled and functionally annotated the BAT proteome. This study will be helpful for future studies focused on biomarker identification and BAT molecular mechanisms.

Cost-Effective Monolithic Hierarchical Carbon Cryogels with Nitrogen Doping and High-Performance Mechanical Properties for CO2 Capture.

Cost-effective nitrogen-doped monolithic hierarchical carbon cryogels with excellent mechanical properties and carbon dioxide (CO2) adsorption performance were prepared from phenol, melamine, and formaldehyde (PMF) by the sol-gel, freeze-drying, and then, pyrolysis processes under an inert atmosphere. The morphology, mechanical properties, pore structure, and chemical characteristics of these cryogels were investigated. The results showed that the dilution ratio played a crucial role in the preparation of nitrogen-doped PMF carbon cryogels with controlled structures. The prepared carbon cryogels were a kind of monolithic materials composed of a hierarchical pore structure and had high compression properties (0.67 and 9.4 MPa for strength and modulus), porosity (97.6%), surface area (1406 m2/g), and heteroatom nitrogen content (0.98-2.09%). CO2 adsorption capacities up to 5.75 mmol/g at 0 °C and 4.50 mmol/g at 25 °C under 1 bar were obtained, which is at a high level among N-doped carbon materials and far better than resorcinol-based carbon gels reported. These superior CO2 adsorption capacities, high isosteric adsorption heat (Qst), and good CO2/N2 adsorption selectivity were ascribed to the synergistic effect of high surface area, appropriate pore size, and also heteroatom doping.

Effects of metformin on metabolism of white and brown adipose tissue in obese C57BL/6J mice.

BACKGROUND: To investigate effects of metformin on the regulation of proteins of white adipose tissue (WAT) and brown adipose tissue (BAT) in obesity and explore the underlying mechanisms on energy metabolism. METHODS: C57BL/6J mice were fed with normal diet (ND, n = 6) or high-fat diet (HFD, n = 12) for 22 weeks. HFD-induced obese mice were treated with metformin (MET, n = 6). After treatment for 8 weeks, oral glucose tolerance test (OGTT) and hyperinsulinemic-euglycemic clamp were performed to evaluate the improvement of glucose tolerance and insulin sensitivity. Protein expressions of WAT and BAT in mice among ND, HFD, and MET group were identified and quantified with isobaric tag for relative and absolute quantification (iTRAQ) coupled with 2D LC-MS/MS. The results were analyzed by MASCOT, Scaffold and IPA. RESULTS: The glucose infusion rate in MET group was increased significantly compared with HFD group. We identified 4388 and 3486 proteins in WAT and BAT, respectively. As compared MET to HFD, differential expressed proteins in WAT and BAT were mainly assigned to the pathways of EIF2 signaling and mitochondrial dysfunction, respectively. In the pathways, CPT1a in WAT, CPT1b and CPT2 in BAT were down-regulated by metformin significantly. CONCLUSIONS: Metformin improved the body weight and insulin sensitivity of obese mice. Meanwhile, metformin might ameliorate endoplasmic reticulum stress in WAT, and affect fatty acid metabolism in WAT and BAT. CPT1 might be a potential target of metformin in WAT and BAT.

Comprehensive map and functional annotation of the mouse white adipose tissue proteome.

White adipose tissue (WAT) plays a significant role in energy metabolism and the obesity epidemic. In this study, we sought to (1) profile the mouse WAT proteome with advanced 2DLC/MS/MS approach, (2) provide insight into WAT function based on protein functional annotation, and (3) predict potentially secreted proteins. A label-free 2DLC/MS/MS proteomic approach was used to identify the WAT proteome from female mouse WAT. A total of 6,039 proteins in WAT were identified, among which 5,160 were quantified (spanning a magnitude of 106) using an intensity-based absolute quantification algorithm, and 3,117 proteins were reported by proteomics technology for the first time in WAT. To comprehensively analyze the function of WAT, the proteins were divided into three quantiles based on abundance and we found that proteins of different abundance performed different functions. High-abundance proteins (the top 90%, 1,219 proteins) were involved in energy metabolism; middle-abundance proteins (90-99%, 2,273 proteins) were involved in the regulation of protein synthesis; and low-abundance proteins (99-100%, 1,668 proteins) were associated with lipid metabolism and WAT beiging. Furthermore, 800 proteins were predicted by SignalP4.0 to have signal peptides, 265 proteins had never been reported, and five have been reported as adipokines. The above results provide a large dataset of the normal mouse WAT proteome, which might be useful for WAT function research.

[Unusual Isolated Sellar Spindle Cell Carcinoma:Report of One Case].

Sellar malignant tumors are uncommon and usually reported as metastatic diseases from breast or lung cancers. Spindle cell carcinoma (SCC) is a rare malignancy and has been found in breast,oral cavity,lungs,kidneys,and hepatobiliary pancreatic system but not in sellar region. We report here the first case of isolated sellar SCC with aggressive features in Peking Union Medical College Hospital. This patient was referred to our hospital on September 9,2015 and discharged on October 16,2015. We described the clinical manifestations,imaging findings,and pathological features of this rare disease.

A Risk Factor Analysis of Cognitive Impairment in Elderly Patients with Chronic Diseases in a Chinese Population.

BACKGROUND This study analyzed the risk factors of cognitive impairment (CI) in elderly patients with chronic diseases. MATERIAL AND METHODS In total of 385 elderly patients with chronic diseases were selected and assigned into CI and normal groups. The activities of daily living (ADL), global deterioration scale (GDS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), patient-generated subjective global assessment (PG-SGA), and mini nutritional assessment (MNA) were performed to analyze the differences between the 2 groups. Logistic regression analysis was conducted for risk factors of CI in elderly patients with chronic diseases. RESULTS There were differences in age, education level, type 2 diabetes mellitus, multifocal cerebral infarction, hearing, and eyesight between CI and normal groups. Patients in the CI group showed more CD4+ cells, more admission times, and higher GDS scores than the normal group. Also, MMSE and MoCA scores revealed differences in total score, directive force, attention and calculating ability, language, delayed memory, reading comprehension, writing, and visual-spatial ability between the 2 groups. The number of B and CD8+ cells, ADL, and MNA scores were protective factors, while cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age were risk factors of CI in elderly patients with chronic diseases. CONCLUSIONS Our study provides evidence that cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age are risk factors of CI in elderly patients with chronic diseases.

Prevalence of dyslipidemia and its control in type 2 diabetes: A multicenter study in endocrinology clinics of China.

OBJECTIVE: The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China. MATERIALS AND METHODS: A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. RESULTS: In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. CONCLUSION: The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients.

Advances in Glycemic Characteristics, Complications, and Treatment for Patients Undergoing Total Pancreatectomy.

Total pancreatectomy has been mainly used to treat malignant diseases of the pancreas, di-ffuse ductal involvement, and severe chronic pancreatitis. Patients may develop pancreatic diabetes after the surgery, in whom the glucose levels fluctuate widely and are hard to control, which increases the incidence of recurrent hypoglycemia. Postoperative complications are closely associated with the glucose levels. Thus, tighter glycemic management is essential for increasing the survival of these patients. Few cases have been discribed in China. In this article, we reviewed the blood glucose features, peri- and post-operative complications, and clinical treatment for patients undergoing total pancreatectomy.

[Application of Three Dimensional Confocal Micro X-Ray Fluorescence Technology Based on Polycapillary X-Ray Lens in Analysis of Rock and Mineral Samples].

Confocal three dimensional (3D) micro X-ray fluorescence (XRF) spectrometer based on a polycapillary focusing X-ray lens (PFXRL) in the excitation channel and a polycapillary parallel X-ray lens (PPXRL) in the detection channel was developed. The PFXRL and PPXRL were placed in a confocal configuration. This was helpful in improving the signal-to-noise ratio of the XRF spectra, and accordingly lowered the detection limitation of the XRF technology. The confocal configuration ensured that only the XRF signal from the confocal micro-volume overlapped by the output focal spot of the PFXRL and the input focal spot of the PPXRL could be detected by the detector. Therefore, the point-to-point information of XRF for samples could be obtained non-destructively by moving the sample located at the confocal position. The magnitude of the gain in power density of the PFXRL was 10(3). This let the low power conventional X-ray source be used in this confocal XRF, and, accordingly, decreased the requirement of high power X-ray source for the confocal XRF based on polycapillary X-ray optics. In this paper, we used the confocal 3D micro X-ray fluorescence spectrometer to non-destructively analyzed mineral samples and to carry out a 3D point-to-point elemental mapping scanning, which demonstrated the capabilities of confocal 3D micro XRF technology for non-destructive analysis elements composition and distribution for mineral samples. For one mineral sample, the experimental results showed that the area with high density of element of iron had high density of copper. To some extent, this reflected the growth mechanisms of the mineral sample. The confocal 3D micro XRF technology has potential applications in such fields like the analysis identification of ore, jade, lithoid utensils, "gamble stone" and lithoid flooring.

Effects of Estrogen on Insulin Sensitivity and Adipokines in Mice.

OBJECTIVE: To study the potential mechanisms via which estrogen exerts its effects on the insulin sensitivity in mice. METHODS: Totally 36 female C57BL/6J mice aged 6 weeks were randomly divided into six groups:normal diet (NOR) group, normal diet with ovariectomy (NOR+OVX) group, normal diet with ovariectomy and estrogen replacement (NOR+OVX+E2) group,high-fat diet (HF) group, high-fat diet with ovariectomy (HF+OVX) group, and high-fat diet with ovariectomy and estrogen replacement (HF+OVX+E2) group. There were six mice in each group. After the ovariectomy based on the grouping, the mice were given normal diet or high-fat diet for 20 weeks. The intervention groups were given estrogen (5 µg/d,subcutaneous injection) for 20 days. Then,the body weight,visceral fat weight,oral glucose tolerance and insulin sensitivity (by euglycemic hyperinsulinemic clamp test), and serum leptin, adiponectin,and resistin levels were compared among these six groups. RESULTS: Compared with HF group, the HF+OVX group had significantly higher body weight and visceral fat weight and lower glucose tolerance, which were significantly improved after estrogen replacement therapy (all P<0.05). However, these indicators showed no significant differences among groups with normal diets (all P>0.05). The insulin sensitivity of ovariectomized mice was significantly decreased in both high-fat and normal diet groups and was also improved significantly after estrogen replacement (P<0.05). The serum leptin was increased and adiponectin was decreased significantly in ovariectomized mice, and the improvements of these two adipokines were also statistically significant after estrogen therapy (P<0.05): however,the serum resistin level was not significantly different among these 6 groups (P>0.05). CONCLUSIONS: Estrogen replacement therapy can improve insulin resistance by lowering body weight. In addition, it can exert its effect directly on adipose tissue,improve the levels of adipokines,reduce the amount of visceral fat, and improve insulin sensitivity in mice.

Comparative proteome analysis of brown adipose tissue in obese C57BL/6J mice using iTRAQ-coupled 2D LC-MS/MS.

High-fat diet (HFD) leads to the development of obesity accompanied by insulin resistance, which increases the risk of type 2 diabetes mellitus and cardiovascular disease. Brown adipose tissue (BAT) plays an essential role in energy metabolism, thus it will give us promising treatment targets through elucidating underlying mechanisms of BAT in obesity. In this study, female C57BL/6J mice were fed HFD or normal diet (ND) for 22 weeks. Hyperinsulinemic-euglycemic clamp was performed to evaluate insulin sensitivity, which was independently correlated with obesity. Using isobaric tag for relative and absolute quantification (iTRAQ) coupled with 2D LC-MS/MS, we quantitated 3048 proteins in BAT. As compared HFD with ND, we obtained 727 differentially expressed proteins. Functional analysis found that those proteins were mainly assigned to the pathway of mitochondrial function. In this pathway, carnitine O-palmitoyltransferase 2 (CPT2), uncoupling protein 1 (UCP1) and apoptosis-inducing factor 1 (AIF1) were up-regulated significantly by HFD, and they were confirmed by western blotting. The results indicated that HFD might induce the apoptosis of brown adipocytes via the up-regulated AIF1. Meanwhile, HFD also stimulated fatty acid ß-oxidation and raised compensatory energy consuming through the increases of CPT2 and UCP1, respectively. However, the apoptosis of brown adipocytes might weaken the compensatory energy expenditure, and finally contribute to overweight/obesity. So, preventing the apoptosis of brown adipocytes may be the key target to treat obesity.

[Application of confocal technology based on polycapillary X-ray lens in measuring thickness].

A confocal micro X-ray fluorescence thickness gauge based on a polycapillary focusing X-ray lens, a polycapillary parallel X-ray lens and a laboratory X-ray source was designed in order to analyze nondestructively the thickness of thin film and cladding material. The performances of this confocal thickness gauge were studied. Two Ni films with a thickness of about 25 and 15 microm respectively were measured. The relative errors corresponding to them were 3.5% and 7.1%, respectively. The thickness uniformity of a Ni films with a thickness of about 10 microm was analyzed. This confocal technology for measuring the thickness was both spatially resolved and elemental sensitive, and therefore, it could be used to measure the thickness of the multilayer sample and analyze the thickness uniformity of the sample. This confocal thickness gauge had potential applications in analyzing the thickness of sample.

[Application of confocal micro-beam X-ray fluorescence in nondestructive scanning analysis of the distribution of elements in a single hair].

The confocal micro X-ray fluorescence (XRF) based on polycapillary X-ray lens and conventional X-ray source was used to carry out the scanning analysis of the distribution of the elements in a single hair. The elemental distribution in the single hair was obtained. In the confocal micro XRF technology, the output focal spot of the polycapillary focusing X-ray lens and the input focal spot of the polycapillary parallel X-ray lens were adjusted confocally. The detector could only detect the X-rays from the overlapping foci. This confocal structure decreased the effects of the background on the X-ray spectra, and was accordingly helpful for improving the accuracy of this XRF technology. A polycapillary focusing X-ray lens with a high gain in power density was used to decrease the requirement of power of the X-ray source used in this confocal technology, and made it possible to perform such confocal micro XRF analysis by using the conventional X-ray source with low cost. Experimental results indicated that the confocal micro X-ray fluorescence based on polycapillary X-ray lens had potential applications in analyzing the elemental distribution of individual hairs.

rs4215 SNP in zinc-α2-glycoprotein gene is associated with obesity in Chinese north Han population.

OBJECTIVE: Zinc-α2-glycoprotein (ZAG) has been identified recently as a novel adipokine due to its close link with lipid and glucose metabolism, as well as regulation of body weight. The aim of our present study is to investigate the ZAG genetic polymorphism association with obesity in Chinese north Han population. DESIGN AND METHODS: Five SNPs of ZAG gene including rs2247607 (A>T), rs4727442 (G>T), rs4215 (A>G), rs2527923 (C>T) and rs2527882 (C>T) were genotyped in 648 overweight/obese patients and 313 healthy controls by TaqMan-PCR methods. Crosstabs statistical analysis method with subjects stratifying by age (≦ 30 y, 31-45 y, ≧ 46 y) and gender was used. RESULTS: The results showed the constitution of three genotype frequencies in rs4215 (A>G) site significantly differs in male subgroup (aged 31-45 y) between overweight/obese and healthy control group (χ(2)=6.401, P=0.041). GG genotype frequency in overweight/obese group is 19.3% which is much higher than 6.1% in healthy control group. Further statistical analysis under a recessive inheritance model demonstrated odd ratio (OR) for GG vs. AA+AG in overweight/obese group was 3.674 (95% CI 1.049-12.866; P=0.035). Among three genotypes of rs4215, the subjects with GG genotype have much more higher body weight, BMI, waist circumference and SBP. CONCLUSION: Our data, for the first time, suggest the genotypes of rs4215 in ZAG gene are significantly associated with obesity in Chinese north Han population. GG genotype subjects in rs4215 site have an increased susceptibility to obesity when compared with the AA+AG genotype subjects.

Rare case of reninoma with double inferior vena cava.

A 16-year-old boy suffered from headaches and dizziness for 2 years. He was found to have remarkably elevated blood pressure (BP) of 180/110 mmHg. Laboratory findings showed a low level of serum potassium and markedly increased plasma renin activity. A solid mass at the periphery of the right kidney and double inferior vena cava (IVC) were detected by abdominal computer tomography (CT). Right partial nephrectomy via laparoscopy was performed on the patient. The histologic and electron microscopic findings comfirmed a diagnosis of juxtaglomerlar cell tumor. The patient had no headache or dizziness with normal BP after surgery.

Generalized glucocorticoid resistance accompanied with an adrenocortical adenoma and caused by a novel point mutation of human glucocorticoid receptor gene.

BACKGROUND: Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. This syndrome is partially caused by mutations in the human glucocorticoid receptor (hGR) gene. The clinical spectrum of generalized glucocorticoid resistance is broad, ranging from fatigue or no symptoms to severe hypertension with hypokalemic alkalosis. The purpose of this study was to explore the genetic disorder of glucocorticoid resistance syndrome. METHODS: We identified a 56-year-old male patient diagnosed with generalized glucocorticoid resistance syndrome accompanied with an adrenocortical adenoma. This asymptomatic patient referred to Peking Union Medical College Hospital for treatment of his adrenal incidentaloma. Endocrinological evaluation consistently revealed his elevated serum cortisol level. Total RNA was extracted from the patient's peripheral blood mononuclear leukocytes (PBMLs) and entire coding region of hGR alpha was amplified by reverse transcription (RT)-PCR. To confirm the possible mutation identified by sequencing RT-PCR products, genomic DNA sequence of hGR gene from the patient and 50 healthy controls was analyzed by PCR and directly sequencing. RESULTS: A heterozygotic (C→T) substitution at nucleotide position of 1667 (exon 5) in GR alpha gene was found in this patient by sequencing of RT-PCR products of hGR gene. This substitution was also identified at genomic DNA level and it was absent in 100 chromosomes from 50 unrelated health controls. This substitution resulted in a threonine to isoleucine substitution (ACT→ATT) at amino acid 556 in the ligand-binding domain of GR alpha. CONCLUSION: Generalized glucocorticoid resistance in this patient might be caused by a novel heterozygotic mutation in the ligand-binding domain of the GR alpha.

[Clinical features of 9 patients with X-linked adrenal hypoplasia congenita caused by DAX1/NR0B1 gene mutations].

OBJECTIVE: To study the clinical features of 9 patients with X-linked adrenal hypoplasia congenita (AHC) by gene sequencing so as to provide diagnostic rationales. METHODS: The patients were 9 cases of X-linked AHC treated at our hospital from July 2007 to June 2009. The clinical manifestations were analyzed. The blood biochemistry tests and the hormone examinations including luteinizing hormone-releasing hormone (LHRH) stimulation tests and human chorionic gonadotropin (HCG) stimulation tests were conducted to evaluate the functions of gonads. And CT scans of adrenal glands and gene tests of DAX1/NR0B1 were performed. RESULTS: Nine AHC patients from 8 families were studied. All patients had DAX1/NR0B1 gene mutations. The main clinical features were: (1) some patients (3 families) had a family history of X-linked recessive inheritance; (2) the ages of onset were all below 10 years old (from 2 month after birth to 9 years old) and ages of being treated at our hospital were from 15 to 34 years old; (3) all patients had adrenocortical hypofunctions, but clinical situations were different, most of them had pigmentation (n = 9), nausea and vomiting (n = 8), hypotension (n = 6), Addisonian crisis (n = 4). Others were debility, hypoglycemia and cold susceptibility. Laboratory tests indicated that all patients had hyponatremia at the onset and higher blood adrenocorticotropic hormone level, lower blood 17-hydroxyprogesterone level compared to normal controls; (4) none of the patients had puberty and there was no responses to LHRH stimulation tests, 3 of them had normal responses to HCG stimulation tests; (5) small bilateral adrenal glands were displayed on CT scans. CONCLUSIONS: The main clinical features of X-linked AHC are adrenocortical hypofunction and hypogonadotropic hypogonadism. But the phenotypes vary greatly in different patients. So male children with adrenal cortical hypofunction should be suspected of X-linked AHC and DAX1/NR0B1 gene tests should be performed. The sexual development of the patients also should be followed up.

Association between four adipokines and insulin sensitivity in patients with obesity, type 1 or type 2 diabetes mellitus, and in the general Chinese population.

BACKGROUND: Hyperinsulinemic 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. METHODS: In 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. RESULTS: There 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. CONCLUSION: Only 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.

[Mechanism, treatment, and evaluation of obesity-induced insulin resistance and type 2 diabetes].

Obesity is a major cause of insulin resistance and type 2 diabetes. The altered glucose homeostasis is caused by faulty insulin signal transduction, which results in decreased glucose uptake by the muscle, altered lipogenesis, and increased glucose output by the liver. The etiology of this derangement in insulin signaling is related to a chronic inflammatory state, leading to the induction of inducible nitric oxide synthase and release of high levels of nitric oxide and reactive nitrogen species, which together cause posttranslational modifications in the signaling proteins. There are substantial differences in the molecular mechanisms of insulin resistance in muscle versus liver. Hormones and cytokines from adipocytes can enhance or inhibit both glycemic sensing and insulin signaling. The role of the central nervous system in glucose homeostasis also has been well established. Multi-pronged therapies aimed at rectifying obesity induced anomalies in both central nervous system and peripheral tissues may prove to be beneficial. The golden standard method to evaluate the insulin sensitivity is hyperinsulinemic euglycemic clamp.