Objective: Resistin has been linked with obesity and hypothesized as a potential marker of insulin resistance in addition to being linked with acute inflammation. However, these links are still highly controversial in humans. Our goal was to examine resistin levels in relation to obesity, insulin resistance and inflammation markers in a large population of Asian children and adolescents. Methods: Children and adolescents (n ¼ 3472) aged 6-18 years, boys (n ¼ 1765) and girls (n ¼ 1707), were assessed for body size parameters, pubertal development, blood lipids, glucose, insulin, resistin, C-reactive protein (CRP), adiponectin and complement C3 (C3) levels. Results: Resistin increased with central obesity in both genders but not with simple adiposity in boys. Several markers associated with central obesity correlated in a gender-specific fashion with plasma resistin. Waist circumference, fat-mass percentage, waistto-height ratio and body mass index (BMI) positively correlated with resistin in both genders. Blood lipids such as triglycerides, nonesterified fatty acids (NEFA) and low-density lipoprotein cholesterol, diastolic and systolic blood pressure correlated positively with resistin in boys. NEFA, high-density lipoprotein cholesterol (negatively) and inflammation markers, such as CRP and C3, positively correlated with resistin in girls. There was no correlation between resistin and adiponectin, and no association of adiponectin with resistin quintiles in either boys or girls. In both boys and girls, resistin tended to decrease with age, with girls having higher levels than boys. Few indices of insulin resistance were linked with plasma resistin in either gender. Conclusion: In this population, plasma resistin levels are a weak biochemical marker of metabolic dysfunction defined by central obesity, adiposity and inflammation and does not predict insulin resistance. Only a small proportion of resistin variation can be explained by factors related to metabolic syndrome, suggesting that resistin is not strongly implicated in a concentrationdependent fashion in any of the examined pathologies.

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Acylation-stimulating protein (C3adesArg/ASP) is an adipokine that acts on its receptor C5L2 to stimulate triglyceride (TG) synthesis in adipose tissue. The present study investigated ASP levels in mouse models of obesity and leanness and the effect of ASP deficiency in C3 knockout (C3KO) mice on adipose tissue morphology. Plasma ASP levels in wild-type (WT) mice correlated positively with plasma nonesterified fatty acids (NEFA) (R ϭ 0.664, P Ͻ 0.001) and total cholesterol (R ϭ 0.515, P Ͻ 0.001). Plasma ASP was increased by 85% in obese ob/ob leptin-deficient mice and decreased in lean diacylglycerol acyltransferase 1 (DGAT1) KO mice (Ϫ54%) and C/EBP␣ ␤/␤ transgenic mice (Ϫ70%) compared with WT. Mice lacking alternative complement factor B or adipsin (FBKO or ADKO), required for ASP production, were also ASP deficient. Both FBKO and C3KO mice had delayed postprandial TG and NEFA clearance on low-fat (LF) and high-fat (HF) diets, suggesting that lack of ASP, not C3, drives the metabolic phenotype. Adipocyte size distribution in C3KO mice was polarized (increased number of both small and large cells), with decreased adipsin expression (Ϫ33% gonadal HF), DGAT1 expression (Ϫ31% to Ϫ50%) and DGAT activity (Ϫ41%). Overall, a reduction/deficiency in ASP is associated with an antiadipogenic state and ASP may provide a target for controlling fat storage. C3adesArg; complement C3; factor B; diacylglycerol acyltransferase 1; postprandial lipemia ACYLATION-STIMULATING PROTEIN (ASP/C3adesArg) is an adipose tissue-derived hormone that stimulates adipocyte triglyceride (TG) synthesis and glucose transport (20, 43). ASP acts through its receptor C5L2, a G protein-coupled receptor, to stimulate diacylglycerol acyltransferase (DGAT) activity, the rate-limiting enzyme in the TG synthesis pathway, and glucose transport (17,18).It has been suggested that ASP is generated through the alternative pathway of complement activation, based on differentiation-dependent expression of adipsin (factor D), complement C3, and factor B (FB) in adipose tissue (4, 5); however, this has not been shown directly. C3 convertase of the alternative pathway, a proteolytic complex formed by the interaction of C3b, FB, and adipsin (factor D), cleaves the third complement component (C3) into C3a and C3b (8). C3a is a potent anaphylatoxin interacting with its receptor C3aR. However, in the circulation, the terminal arginine of C3a is rapidly cleaved by carboxypeptidase B, inactivating the C3a anaphylatoxic function and generating C3adesArg (ASP) (8). Both ASP/C3adesArg and C3a interact with the receptor C5L2 to effectively stimulate TG synthesis in cultured adipocytes (18).C3 knockout (C3KO) mice are obligatorily ASP deficient, since they lack the precursor protein. We have previously reported that C3KO mice are lean yet hyperphagic (22, 40); the increased energy intake is being balanced by an increased energy expenditure (40). C3KO mice also displayed an altered plasma lipoprotein profile, mainly characterized by delayed postprandial TG clearance (23,24,40)...

Heterogeneous populations of hypothalamic neurons orchestrate energy balance via the release of specific signatures of neuropeptides. However, how specific intracellular machinery controls peptidergic identities and function of individual hypothalamic neurons remains largely unknown. The transcription factor T-box 3 (Tbx3) is expressed in hypothalamic neurons sensing and governing energy status, whereas human TBX3 haploinsufficiency has been linked with obesity. Here we demonstrate that loss of Tbx3 function in hypothalamic neurons causes weight gain and other metabolic disturbances by disrupting both peptidergic identity and plasticity of Pomc/Cart and Agrp/Npy neurons. These alterations are observed after loss of Tbx3 in both immature hypothalamic neurons and terminally differentiated murine neurons. We further establish the importance of Tbx3 for body weight regulation in Drosophila melanogaster and show that TBX3 is implicated in the differentiation of human embryonic stem cells (hESC) into hypothalamic Pomc neurons. Our data indicate that Tbx3 directs the terminal specification of neurons as functional components of the melanocortin system and is required for maintaining their peptidergic identity. In summary, we report the discovery of a mechanistic key process underlying the functional heterogeneity of hypothalamic neurons governing body weight and systemic metabolism.