Ethnic differences in beta-cell function, dietary intake and expression of the metabolic syndrome among UK adults of south Asian, black African-Caribbean and white-European origin at high risk of metabolic syndrome

A cross-sectional analysis of ethnic differences in dietary intake, insulin sensitivity and beta-cell function, using the intravenous glucose tolerance test (IVGTT), was conducted on 497 healthy adult participants of the ‘Reading, Imperial, Surrey, Cambridge, and Kings’ (RISCK) study. Insulin sensitivity (Si) was significantly lower in African-Caribbean (AC) and South Asian (SA) participants [IVGTT-Si; AC: 2.13 vs SA: 2.25 vs white-European (WE): 2.84 (×10−4 mL µU min)2, p < 0.001]. AC participants had a higher prevalence of anti-hypertensive therapy (AC: 19.7% vs SA: 7.5%), the most cardioprotective lipid profile [total:high-density lipoprotein (HDL); AC: 3.52 vs SA: 4.08 vs WE: 3.83, p = 0.03] and more pronounced hyperinsulinaemia [IVGTT–acute insulin response (AIR)] [AC: 575 vs SA: 428 vs WE: 344 mL/µU/min)2, p = 0.002], specifically in female participants. Intake of saturated fat and carbohydrate was lower and higher in AC (10.9% and 50.4%) and SA (11.1% and 52.3%), respectively, compared to WE (13.6% and 43.8%, p < 0.001). Insulin resistance in ACs is characterised by ‘normal’ lipid profiles but high rates of hypertension and pronounced hyperinsulinaemia.

Gene-nutrient interactions on the phosphoenolpyruvate carboxykinase influence insulin sensitivity in metabolic syndrome subjects

Genetic background may interact with habitual dietary fat composition, and affect development of the metabolic syndrome (MetS). The phosphoenolpyruvate carboxykinase gene (PCK1) plays a significant role regulating glucose metabolism, and fatty acids are key metabolic regulators, which interact with transcription factors and influence glucose metabolism. We explored genetic variability at the PCK1 gene locus in relation to degree of insulin resistance and plasma fatty acid levels in MetS subjects. Moreover, we analyzed the PCK1 gene expression in the adipose tissue of a subgroup of MetS subjects according to the PCK1 genetic variants.

Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia

Abstract Objective: Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia. Methods: Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t=0 min) and lunch (t=330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples. Results: MetS subjects with 3 or 4 components were subdivided into those without (n=34) and with (n=23) fasting hyperglycaemia (≥ 5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (P<0.001). Following the test meals, there was a higher maximum concentration (maxC), area under the curve (AUC) and incremental AUC (P≤0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (P<0.001) and insulin maxC (P=0.010) was also observed in these individuals after the test meals. Multivariate regression analysis revealed fasting glucose to be an important predictor of the postprandial TAG and glucose response. Conclusion: Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia.

A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults

Metabolic syndrome is a set of disorders that increases the risk of developing cardiovascular disease. The gut microbiota is altered toward a less beneficial composition in overweight adults and this change can be accompanied by inflammation. Prebiotics such as galactooligosaccharides can positively modify the gut microbiota and immune system; some may also reduce blood lipids. We assessed the effect of a galactooligosaccharide mixture [Bi2 muno (B-GOS)] on markers of metabolic syndrome, gut microbiota, and immune function in 45 overweight adults with $3 risk factors associated with metabolic syndrome in a double-blind, randomized, placebo (maltodextrin)-controlled, crossover study (with a 4-wk wash-out period between interventions). Whole blood, saliva, feces, and anthropometric measurements were taken at the beginning, wk 6, and end of each 12-wk intervention period. Predominant groups of fecal bacteria were quantified and full blood count, markers of inflammation and lipid metabolism, insulin, and glucose were measured. B-GOS increased the number of fecal bifidobacteria at the expense of less desirable groups of bacteria. Increases in fecal secretory IgA and decreases in fecal calprotectin, plasma C-reactive protein, insulin, total cholesterol (TC), TG, and the TC:HDL cholesterol ratio were also observed. Administration of B-GOS to overweight adults resulted in positive effects on the composition of the gut microbiota, the immune response, and insulin, TC, and TG concentrations. B-GOSmay be a useful candidate for the enhancement of gastrointestinal health, immune function, and the reduction of metabolic syndrome risk factors in overweight adults.

Absence of Association of Metabolic Syndrome with PPARGC1A, PPARG and UCP1 Gene Polymorphisms in Asian Indians

The objective of this study was to evaluate the association of PPARG coactivator1 alpha (PPARGC1A), peroxisome proliferator activated receptor gamma (PPARG), and uncoupling protein1 (UCP1) gene polymorphisms with the metabolic syndrome (MS) in an Asian Indian population. Nine common polymorphisms were genotyped via polymerase chain reaction restriction fragment length polymorphism and direct sequencing in 950 normal glucose-tolerant subjects and 550 type 2 diabetic subjects, chosen randomly from the Chennai Urban Rural Epidemiological Study, an ongoing population based study in Southern India. Among the 9 polymorphisms examined, only the Thr394Thr variant of the PPARGC1A gene was significantly associated with diabetes and obesity. The genotype frequency of GA of Thr394Thr variant was 16% (138/887) in the nonMS group and 22% (136/613) in the MS group, and this genotype frequency was significantly higher with MS both in males (p = 0.01) and females (p = 0.05), compared to the without-MS group. Logistic regression analysis revealed that the odds ratio for MS for the susceptible genotype GA of Thr394Thr was 1.411 [95% CI: 1.03-1.84, p = 0.012]. In the multiple logistic regression analysis, however, there was no association of this polymorphism as an independent factor with MS. Hence, the study shows that the polymorphisms in the PPARGC1A, PPARG and UCP1 genes are not associated with MS in Asian Indians.

Thr54 allele carriers of the Ala54Thr variant of FABP2 gene have associations with metabolic syndrome and hypertriglyceridemia in urban South Indians

The intestinal fatty acid-binding protein gene is proposed as a candidate gene for diabetes because the protein it codes is involved in fatty acid absorption and metabolism. This study investigates the association of the Ala54Thr variant of the intestinal fatty acid-binding protein gene on type 2 diabetes mellitus and other related metabolic traits in Asian Indians. Ala54Thr polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism in unrelated 773 type 2 diabetic and 899 normal glucose-tolerant (NGT) subjects, randomly chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in South India. The Ala54Thr polymorphism was not associated with type 2 diabetes mellitus or obesity. However, genotype-phenotype study revealed that the NGT subjects carrying the Thr54 allele had significantly higher 2-hour plasma glucose (P = .007), glycated hemoglobin (P = .004), 2-hour insulin (P = .027), and fasting low-density lipoprotein cholesterol (P = .032) levels compared with those with the Ala54 allele. Normal glucose-tolerant subjects with Ala54Thr and Thr54Thr genotypes had significantly higher fasting serum triglyceride levels (P = .003) compared with those with Ala54Ala. The subjects were stratified into those with hypertriglyceridemia (serum triglyceride levels >or=150 mg/dL) and those without. The odds ratio for hypertriglyceridemia for the individuals carrying the Ala54Thr genotype was 1.491 (95% confidence interval [CI], 1.22-1.83, P < .0001), and for those carrying the Thr54Thr genotype, it was 1.888 (95% CI, 1.34-2.67; P < .0001). Subjects were also stratified into those with metabolic syndrome (MS) and those without, according to modified Adult Treatment Panel III guidelines. The odds ratio (adjusted for age and sex) for MS for the individuals carrying the Ala54Thr genotype was 1.240 (95% CI, 1.02-1.51; P = .03), whereas for those carrying the Thr54Thr genotype, it was 1.812 (95% CI, 1.28-2.57; P = .001). Carriers of the Thr54 allele have associations with MS and hypertriglyceridemia in this urban South Indian population.

Association of low adiponectin levels with the metabolic syndrome--the Chennai Urban Rural Epidemiology Study (CURES-4)

The aim of the study was to assess the relation of adiponectin levels with the metabolic syndrome in Asian Indians, a high-risk group for diabetes and premature coronary artery disease. The study was conducted on 100 (50 men and 50 women) type 2 diabetic subjects and 100 age and sex matched subjects with normal glucose tolerance selected from the Chennai Urban Rural Epidemiology Study, an ongoing population study in Chennai in southern India. Metabolic syndrome was defined using modified Adult Treatment Panel III (ATPIII) guidelines. Adiponectin values were significantly lower in diabetic subjects (men: 5.2 vs 8.3 microg/mL, P=.00l; women: 7.6 vs 11.1 microg/mL, P<.00l) and those with the metabolic syndrome (men: 5.0 vs 6.8 microg/mL, P=.01; women: 6.5 vs 9.9 microg/mL, P=.001) compared with those without. Linear regression analysis revealed adiponectin to be associated with body mass index (P<.05), waist circumference (P<.01), fasting plasma glucose (P=.001), glycated hemoglobin (P<.001), triglycerides (P<.00l), high-density lipoprotein (HDL) cholesterol (P<.001), cholesterol/HDL ratio (P<.00l), and insulin resistance measured by homeostasis assessment model (P<.00l). Factor analysis identified 2 factors: factor 1, negatively loaded with adiponectin and HDL cholesterol and positively loaded with triglycerides, waist circumference, and insulin resistance measured by homeostasis assessment model; and factor 2, with a positive loading of waist circumference and systolic and diastolic blood pressure. Logistic regression analysis revealed adiponectin to be negatively associated with metabolic syndrome (odds ratio [OR], 0.365; P<.001) even after adjusting for age (OR, 0.344; P<.00l), sex (OR, 0.293; P<.001), and body mass index (OR, 0.292; P<.00l). Lower adiponectin levels are associated with the metabolic syndrome per se and several of its components, particularly, diabetes, insulin resistance, and dyslipidemia in this urban south Indian population.

Endocannabinoids, FOXO and the metabolic syndrome: redox, function and tipping point--the view from two systems

The endocannabinoid system (ECS) was only 'discovered' in the 1990s. Since then, many new ligands have been identified, as well as many new intracellular targets--ranging from the PPARs, to mitochondria, to lipid rafts. It was thought that blocking the CB-1 receptor might reverse obesity and the metabolic syndrome. This was based on the idea that the ECS was dysfunctional in these conditions. This has met with limited success. The reason may be that the ECS is a homeostatic system, which integrates energy seeking and storage behaviour with resistance to oxidative stress. It could be viewed as having thrifty actions. Thriftiness is an innate property of life, which is programmed to a set point by both environment and genetics, resulting in an epigenotype perfectly adapted to its environment. This thrifty set point can be modulated by hormetic stimuli, such as exercise, cold and plant micronutrients. We have proposed that the physiological and protective insulin resistance that underlies thriftiness encapsulates something called 'redox thriftiness', whereby insulin resistance is determined by the ability to resist oxidative stress. Modern man has removed most hormetic stimuli and replaced them with a calorific sedentary lifestyle, leading to increased risk of metabolic inflexibility. We suggest that there is a tipping point where lipotoxicity in adipose and hepatic cells induces mild inflammation, which switches thrifty insulin resistance to inflammation-driven insulin resistance. To understand this, we propose that the metabolic syndrome could be seen from the viewpoint of the ECS, the mitochondrion and the FOXO group of transcription factors. FOXO has many thrifty actions, including increasing insulin resistance and appetite, suppressing oxidative stress and shifting the organism towards using fatty acids. In concert with factors such as PGC-1, they also modify mitochondrial function and biogenesis. Hence, the ECS and FOXO may interact at many points; one of which may be via intracellular redox signalling. As cannabinoids have been shown to modulate reactive oxygen species production, it is possible that they can upregulate anti-oxidant defences. This suggests they may have an 'endohormetic' signalling function. The tipping point into the metabolic syndrome may be the result of a chronic lack of hormetic stimuli (in particular, physical activity), and thus, stimulus for PGC-1, with a resultant reduction in mitochondrial function and a reduced lipid capacitance. This, in the context of a positive calorie environment, will result in increased visceral adipose tissue volume, abnormal ectopic fat content and systemic inflammation. This would worsen the inflammatory-driven pathological insulin resistance and inability to deal with lipids. The resultant oxidative stress may therefore drive a compensatory anti-oxidative response epitomised by the ECS and FOXO. Thus, although blocking the ECS (e.g. via rimonabant) may induce temporary weight loss, it may compromise long-term stress resistance. Clues about how to modulate the system more safely are emerging from observations that some polyphenols, such as resveratrol and possibly, some phytocannabinoids, can modulate mitochondrial function and might improve resistance to a modern lifestyle.

Obesity, diabetes and longevity in the Gulf: is there a Gulf Metabolic Syndrome?

The Gulf is experiencing a pandemic of lifestyle-induced obesity and type 2 diabetes mellitus (T2DM), with rates exceeding 50 and 30%, respectively. It is likely that T2DM represents the tip of a very large metabolic syndrome iceberg, which precedes T2DM by many years and is associated with abnormal/ectopic fat distribution, pathological systemic oxidative stress and inflammation. However, the definitions are still evolving with the role of different fat depots being critical. Hormetic stimuli, which include exercise, calorie restriction, temperature extremes, dehydration and even some dietary components (such as plant polyphenols), may well modulate fat deposition. All induce physiological levels of oxidative stress, which results in mitochondrial biogenesis and increased anti-oxidant capacity, improving metabolic flexibility and the ability to deal with lipids. We propose that the Gulf Metabolic Syndrome results from an unusually rapid loss of hormetic stimuli within an epigenetically important time frame of 2-3 generations. Epigenetics indicates that thriftiness can be programmed by the environment and passed down through several generations. Thus this loss of hormesis can result in continuation of metabolic inflexibility, with mothers exposing the foetus to a milieu that perpetuates a stressed epigenotype. As the metabolic syndrome increases oxidative stress and reduces life expectancy, a better descriptor may therefore be the Lifestyle-Induced Metabolic Inflexibility and accelerated AGEing syndrome – LIMIT-AGE. As life expectancy in the Gulf begins to fall, with perhaps a third of this life being unhealthy – including premature loss of sexual function, it is vital to detect evidence of this condition as early in life as possible. One effective way to do this is by detecting evidence of metabolic inflexibility by studying body fat content and distribution by magnetic resonance (MR). The Gulf Metabolic Syndrome thus represents an accelerated form of the metabolic syndrome induced by the unprecedented rapidity of lifestyle change in the region, the stress of which is being passed from generation to generation and may be accumulative. The fundamental cause is probably due to a rapid increase in countrywide wealth. This has benefited most socioeconomic groups, resulting in the development of an obesogenic environment as the result of the rapid adoption of Western labour saving and stress relieving devices (e.g. cars and air conditioning), as well as the associated high calorie diet.

Impact of geographical region on urinary metabolomic and plasma fatty acid profiles in subjects with the metabolic syndrome across Europe: the LIPGENE study

The application of metabolomics in multi-centre studies is increasing. The aim of the present study was to assess the effects of geographical location on the metabolic profiles of individuals with the metabolic syndrome. Blood and urine samples were collected from 219 adults from seven European centres participating in the LIPGENE project (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis). Nutrient intakes, BMI, waist:hip ratio, blood pressure, and plasma glucose, insulin and blood lipid levels were assessed. Plasma fatty acid levels and urine were assessed using a metabolomic technique. The separation of three European geographical groups (NW, northwest; NE, northeast; SW, southwest) was identified using partial least-squares discriminant analysis models for urine (R 2 X: 0•33, Q 2: 0•39) and plasma fatty acid (R 2 X: 0•32, Q 2: 0•60) data. The NW group was characterised by higher levels of urinary hippurate and N-methylnicotinate. The NE group was characterised by higher levels of urinary creatine and citrate and plasma EPA (20 : 5 n-3). The SW group was characterised by higher levels of urinary trimethylamine oxide and lower levels of plasma EPA. The indicators of metabolic health appeared to be consistent across the groups. The SW group had higher intakes of total fat and MUFA compared with both the NW and NE groups (P≤ 0•001). The NE group had higher intakes of fibre and n-3 and n-6 fatty acids compared with both the NW and SW groups (all P< 0•001). It is likely that differences in dietary intakes contributed to the separation of the three groups. Evaluation of geographical factors including diet should be considered in the interpretation of metabolomic data from multi-centre studies.

Top single nucleotide polymorphisms affecting carbohydrate metabolism in Metabolic Syndrome: from the LIPGENE study

Rationale:Metabolic Syndrome (MetS) is a high prevalence condition characterized by altered energy metabolism, insulin resistance and elevated cardiovascular risk.Objectives:Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS.Methods:904 SNPs (tag SNPs and functional SNPs) were tested for influence in eight fasting and dynamic markers of carbohydrate metabolism, performing an intravenous glucose tolerance test in 450 participants of the LIPGENE study.Findings:From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (a 16 % of the pre-selected) remained significant after Bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose: rs26125 (PPARGC1B); fasting insulin: rs4759277 (LRP1); C peptide: rs4759277 (LRP1); HOMA-IR: rs4759277 (LRP1); QUICKI: rs184003 (AGER); SI: rs7301876 (ABCC9), AIRg: rs290481 (TCF7L2) and DI: rs12691 (CEBPA).Conclusions:We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among aproximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

The intelligence paradox; will ET get the metabolic syndrome? Lessons from and for Earth

Mankind is facing an unprecedented health challenge in the current pandemic of obesity and diabetes. We propose that this is the inevitable (and predictable) consequence of the evolution of intelligence, which itself could be an expression of life being an information system driven by entropy. Because of its ability to make life more adaptable and robust, intelligence evolved as an efficient adaptive response to the stresses arising from an ever-changing environment. These adaptive responses are encapsulated by the epiphenomena of “hormesis”, a phenomenon we believe to be central to the evolution of intelligence and essential for the maintenance of optimal physiological function and health. Thus, as intelligence evolved, it would eventually reach a cognitive level with the ability to control its environment through technology and have the ability remove all stressors. In effect, it would act to remove the very hormetic factors that had driven its evolution. Mankind may have reached this point, creating an environmental utopia that has reduced the very stimuli necessary for optimal health and the evolution of intelligence – “the intelligence paradox”. One of the hallmarks of this paradox is of course the rising incidence in obesity, diabetes and the metabolic syndrome. This leads to the conclusion that wherever life evolves, here on earth or in another part of the galaxy, the “intelligence paradox’” would be the inevitable side-effect of the evolution of intelligence. ET may not need to just “phone home” but may also need to “phone the local gym”. This suggests another possible reason to explain Fermi’s paradox; Enrico Fermi, the famous physicist, suggested in the 1950s that if extra-terrestrial intelligence was so prevalent, which was a common belief at the time, then where was it? Our suggestion is that if advanced life has got going elsewhere in our galaxy, it can’t afford to explore the galaxy because it has to pay its healthcare costs.

Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study

Background: Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established. OBJECTIVE: Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors. DESIGN: In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined. RESULTS: Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05). CONCLUSIONS: Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features.

Association of genetic vatiation within UBL5 with phenotypes of metabolic syndrome

The BEACON gene was initially identified using the differential display polymerase chain reaction on hypothalamic mRNA samples collected from lean and obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON gene expression was positively correlated with percentage of body fat, and intracerebroventricular infusion of the Beacon protein resulted in a dose-dependent increase in food intake and body weight. The human homolog of BEACON, UBL5, is located on chromosome 19p in a region previously linked to quantitative traits related to obesity. Our previous studies showed a statistically significant association between UBL5 sequence variation and several obesity- and diabetes-related quantitative physiological measures in Asian Indian and Micronesian cohorts. Here we undertake a replication study in a Mexican American cohort where the original linkage signal was first detected. We exhaustively resequenced the complete gene plus the putative promoter region for genetic variation in 55 individuals and identified five single nucleotide polymorphisms (SNPs), one of which was novel. These SNPs were genotyped in a Mexican American cohort of 900 individuals from 40 families. Using a quantitative trait linkage disequilibrium test, we found significant associations between UBL5 genetic variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals. These data are consistent with our earlier published studies and further support a functional role for the UBL5 gene in influencing physiological traits that underpin the development of metabolic syndrome.

Chemerin is a novel adipokine associated with obesity and metabolic syndrome

Soluble protein hormones are key regulators of a number of metabolic processes, including food intake and insulin sensitivity. We have used a signal sequence trap to identify genes that encode secreted or membrane-bound proteins in Psammomys obesus, an animal model of obesity and type 2 diabetes (T2D). Using this signal sequence trap, we identified the chemokine chemerin as being a novel adipokine. Gene expression of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), was significantly higher in adipose tissue of obese and type 2 diabetic P. obesus compared with lean, normoglycemic P. obesus. Fractionation of P. obesus adipose tissue confirmed that chemerin was predominantly expressed in adipocytes, whereas CMKLR1 was expressed in both adipocytes and stromal-vascular cells of adipose tissue. In 3T3-L1 adipocytes, chemerin was markedly induced during differentiation, whereas CMKLR1 was down-regulated during differentiation. Serum chemerin levels were measured by ELISA in human plasma samples from 114 subjects with T2D and 142 normal glucose tolerant controls. Plasma chemerin levels were not significantly different between subjects with T2D and normal controls. However, in normal glucose tolerant subjects, plasma chemerin levels were significantly associated with body mass index, circulating triglycerides, and blood pressure. Here we report, for the first time, that chemerin is an adipokine, and circulating levels of chemerin are associated with several key aspects of metabolic syndrome.