In the past decade, CW fiber lasers have revolutionized industrial material processing because of their high efficiency, robustness and diffraction-limited beams obtained in kW regimes. However, the output power from a single fiber laser is limited by phenomena such as non-linear effects or excessive heating. To overcome these issues, incoherent beam combining (IBC) of multiple independent fiber lasers has become a common approach for further power scaling, which however comes at the expense of the resulting beam quality. Although the brightness conservation law states that IBC cannot be done without deterioration of the beam quality, minimizing this degradation is of paramount importance to achieve the best performances in material processing applications. The beam quality of a fiber laser is usually characterized by the well-known M 2 parameter, which has a value of 1 for a Gaussian beam and of 1.10 for typical kW single-core fiber lasers. The all-fiber signal combiner (SC), obtained by connecting a tapered fiber bundle (TFB) to a multimode delivery fiber (Fig. 1 (a)), has proven to be a robust approach to realize IBC and reach multi-kW powers [1]. In this work, we investigate the beam quality obtained at the output of a 7×1 SC. The best reported results with such a configuration is a M 2 of 4.6 when the lasers are combined into a 50-μm core multimode fiber and a M 2 of 6.5 when combined into a 100-μm core multimode fiber [2, 3]. In this paper, we experimentally demonstrate the fabrication of a 7×1 SC exhibiting a record lowM 2 of 3.75 into a 50-μm core multimode fiber.
Objective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions. Results. Four clusters gathered genes with similar expression between day 4 to day 7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE, PLIN1, DGAT2, PNPLA2, ADIPOQ, CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for proteins implicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A, KITLG, and FGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1, COL1A2, and COL6A3, MMP1, and TGFB1). Conclusion. Dedifferentiation is associated with downregulation of transcripts encoding proteins involved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cell cycle.
Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05–0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05–0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences.
To evaluate circulating adipokines in people with ketosis‐prone diabetes, a heterogeneous disorder characterized by unprovoked ketoacidosis in people with previously unrecognized diabetes.
Mature adipocytes have been shown to reverse their phenotype into fibroblast-like cells in vitro through a technique called ceiling culture. Mature adipocytes can also be isolated from fresh adipose tissue for depot-specific characterization of their function and metabolic properties. Here, we describe a well-established protocol to isolate mature adipocytes from adipose tissues using collagenase digestion, and subsequent steps to perform ceiling cultures. Briefly, adipose tissues are incubated in a Krebs-Ringer-Henseleit buffer containing collagenase to disrupt tissue matrix. Floating mature adipocytes are collected on the top surface of the buffer. Mature cells are plated in a T25-flask completely filled with media and incubated upside down for a week. An alternative 6-well plate culture approach allows the characterization of adipocytes undergoing dedifferentiation. Adipocyte morphology drastically changes over time of culture. Immunofluorescence can be easily performed on slides cultivated in 6-well plates as demonstrated by FABP4 immunofluorescence staining. FABP4 protein is present in mature adipocytes but down-regulated through dedifferentiation of fat cells. Mature adipocyte dedifferentiation may represent a new avenue for cell therapy and tissue engineering.
Background: The complement system is important in development of atherosclerosis via regulation of lipid and glucose metabolism as well as inflammation. Aim: The aim of the present study was to further analyze the contribution of C5L2 to the development of atherosclerosis. We proposed that, with DIO feeding, C5L2 deficiency would promote a phenotype that encourages atherosclerosis development. Coupled to ApoE deficiency, double knockout (2KO) mice would show exacerbated atherosclerotic plaque formation. Methods: First, Wildtype (WT) and C5L2-/-(C5L2KO) and subsequently, ApoE-/-(ApoEKO) and C5L2/ApoE double knockout mice were placed on diets inducing obesity (DIO) or standard chow diet for 12 - 15 weeks. Plasma lipids, glucose, cytokines and hepatic glycogen and lipid contents, mRNA levels and enzyme activities and atherosclerotic plaque size were measured. Results: C5L2KO had increased hepatic glucose oxidation (+90%, p < 0.001), reduced liver glycogen content on chow diet (-34%, p < 0.05) but increased with DIO (+51%, p < 0.05) vs WT. Glucose clearance was delayed in C5L2/ApoE-2KO vs ApoEKO mice with chow (p < 0.0001) and DIO diet (p = 0.0026). C5L2KO mice had increased hepatic lipid content and fatty acid synthesis but decreased lipid oxidation vs WT. Plasma cholesterol was further elevated in C5L2/ApoE-2KO vs ApoEKO with DIO feeding (p < 0.05). Hepatic cytokine expression was increased in C5L2KO mice compared to WT mice. Atherosclerotic plaque size was increased in C5L2/ ApoE-2KO mice compared with apoEKO on chow (p < 0.05) and DIO regimen (p < 0.001). Conclusions: C5L2 disruption worsens glucose and lipid metabolism, increases hepatic and circulating inflammation, and aggravates atherosclerosis.
ObjectiveBariatric surgery remains the most effective treatment for obesity and metabolic syndrome. Surgical benefit arises from early‐phase resolution of hyperglycemia and late‐phase weight loss. The adipokine chemerin is of interest given its roles in immunity, adipogenesis, and metabolism. The study objective was to examine the effects of biliopancreatic diversion with duodenal switch (BPD‐DS) on plasma chemerin in the early and late post‐operative stages.Methods83 adults with obesity undergoing BPD‐DS, 45 obese non‐surgical controls, and 9 lean surgical controls were enrolled. Plasma parameters and anthropometric measures were obtained at baseline and at, early (24 h, 5 D) and late (6 months and 12 months) post‐operative stages.ResultsPlasma chemerin dropped from 176±49 ng/mL at baseline to 132±52 ng/mL 24 h after BPD‐DS, rebounded to 200±66 ng/mL after 5 D, and declined to 124±51 and 110±34 ng/mL after 6 and 12 months. Plasma chemerin correlated negatively with measures of inflammation and hepatic injury and positively with measures of obesity, metabolic syndrome, and inflammation in the early and late post‐operative periods, respectively.ConclusionsChemerin has a novel role in surgical injury but not hyperglycemia resolution early after BPD‐DS. Over the long term, plasma chemerin declines to a new set point that is partially determined by body fat reductions.
CONTEXT:Orexin is a recently identified neuropeptide hormone.OBJECTIVES:Acute and long-term post-bariatric changes in Orexin and relationship to post-operative metabolic outcomes.DESIGN AND PARTICIPANTS:Men and women undergoing biliopancreatic diversion with duodenal switch bariatric surgery (n = 76, BMI≥35 kg/m(2)) were evaluated for body composition and plasma parameters at baseline, acutely (1 and 5 days) and long-term (6 and 12 months) post-surgery.SETTING:University Hospital Centre, Canada.INTERVENTIONS AND MAIN OUTCOME MEASURES:Groups were subdivided based on acute (average 1 and 5 day) changes in Orexin prior to weight loss: (i)>10% Orexin decrease (n = 33, OrexinDEC) and (ii)>10% Orexin increase (n = 20, OrexinINC), to evaluate impact on long-term changes.RESULTS:Both groups had comparable preoperative Orexin levels, BMI, age, sex distribution, diabetes and lipid lowering medication, plasma glucose and lipid parameters except for apolipoproteinB (p<0.007). Orexin increase was rapid and maintained throughout one year, while OrexinDEC subjects remained significantly lower throughout. Over 12 months, changes in BMI, fat mass, and %fat mass were comparable. Fasting glucose and insulin increased immediately 1-day post-operatively, decreasing rapidly (5-day) and declining thereafter with the OrexinINC group remaining lower than the OrexinDEC group throughout (p = 0.001). Similarly, plasma cholesterol, triglyceride, LDL-C and HDL-C decreased at 1-day, increased slightly (5-day), except HDL-C, then decreased over 1 year, with greater decreases in OrexinINC group relative to OrexinDEC group.CONCLUSION:Rapid postoperative increases in plasma Orexin are associated with better improvement of glucose and lipid profiles following bariatric surgery.
Recent studies suggested that the immunometabolic receptors; C5aR and C5L2, constitutively self-associate into homo-/heterodimers and that acylation stimulating protein (ASP/C3adesArg) or C5a treatment of adipocytes increased their colocalization. The present study evaluates the C5aR contribution in adipocytes to the metabolic and immune responses elicited by ligand stimulation. The effects of C5a, ASP, and insulin on cytokine production, triglyceride synthesis (TGS), and key signaling pathways were evaluated in isolated primary adipocytes and cultured 3T3-L1 differentiated adipocytes. In addition, mRNA expression of IRS1 and PGC1α was compared in adipose tissue samples from WT vs. C5aRKO mice. Both C5a and ASP directly increased MCP-1 (238±4%; P<0.001, and 377±2% vs. basal 100%; P<0.001, respectively) and KC (413±11%; P<0.001, and 529±16%; P<0.001 vs. basal 100%, respectively) secretion, TGS (131±1%; P<0.001, and 152±6%; P<0.001, vs. basal 100% respectively), and Akt/NFκB phosphorylation pathways in adipocytes. However, in C5aRKO adipocytes, C5a effects were disrupted, while stimulatory effects of ASP were mostly maintained. Addition of C5a completely blocked ASP signaling and activity in both C5aRKO and WT adipocytes as well as 3T3-L1 adipocytes. Furthermore, C5aRKO adipocytes revealed impaired insulin stimulation of cytokine production, with partial impairment of signaling and TGS stimulation, consistent with decreased IRS1 and PGC1α mRNA expression in adipose tissue. These observations indicate the importance of C5aR in adipose tissue metabolism and immunity, which may be regulated through heterodimerization with C5L2.
Purpose Vaspin (visceral-adipose-tissue-derived-serine-protease-inhibitor) is a recently identified adipokine with putative insulin-sensitizing properties. Plasma vaspin responses to surgery-induced weight loss are sparse and contradictory. Design and Participants We evaluated changes in vaspin levels and relationship to post-operative outcomes in men (n = 22) and women (n = 55) undergoing biliopancreatic-diversion/duodenal-switch bariatric surgery. Body composition and plasma parameters were measured at baseline, acutely (1 and 5 days) and medium-term (6 and 12 months) post-surgery. Results Fasting preoperative vaspin concentrations were comparable in men vs women. The distribution was biphasic (both men and women) with a nadir of 2.5 ng/ml. Subjects were divided into high (≥2.5 ng/mL, HI-group) and low (<2.5 ng/mL, LO-group) vaspin level. Both groups had comparable sex distribution, age and BMI, but the HI-vaspin group had lower insulin, HOMA, and triglyceride and higher HDL-cholesterol, acylation stimulating protein (ASP) and IL-6 levels (all p<0.05). Post-operatively, both groups decreased BMI comparably over 12 months; the HI-vaspin group maintained high vaspin levels, while the LO-vaspin group gradually increased their levels with weight loss over 12 months. The HI-vaspin group maintained a better glucose, insulin, HOMA, fructosamine, HDL-cholesterol, and triglyceride profile throughout. The HI-vaspin group also had higher gamma-glutamyltransferase and ASP profiles. Finally, baseline vaspin level inversely correlated significantly with baseline and 12-month insulin, HOMA, triglyceride and positively correlated with HDL and ASP. Twelve-month vaspin also correlated similarly, including an inverse correlation with BMI. Conclusion Globally, this study supports the concept of vaspin as a beneficial adipokine in obesity, which may potentially lead to possible therapeutic targets.
The central component of the complement system, C3, is associated with obesity, metabolic syndrome and cardiovascular disease however the underlying reasons are unknown. In the present study we evaluated gene expression of C3, the cleavage product C3a/C3adesArg and its cognate receptor C3aR in subcutaneous and omental adipose tissue in women.Women (n = 140, 21-69 years, BMI 19.5-79 kg/m2) were evaluated for anthropometric and blood parameters, and adipose tissue gene expression.Subjects were separated into groups (n = 34-36) according to obesity: normal/overweight (≤30 kg/m2), obese I (≤45 kg/m2), obese II (≤51 kg/m2), and obese III (≤80 kg/m2). Overall, while omental expression remained unchanged, subcutaneous C3 and C3aR gene expression decreased with increasing adiposity (2-way ANOVA, p<0.01), with a concomitant decrease in SC/OM ratio (p<0.001). In subcutaneous adipose, both C3 and C3aR expression correlated with apoB, and apoA1 and inversely with waist circumference and blood pressure, while C3aR also correlated with glucose (p<0.05-0.0001). While omental C3aR expression did not correlate with any factor, omental C3 correlated with waist circumference, glucose and apoB (all p<0.05). Further, while plasma C3a/C3adesArg increased and adiponectin decreased with increasing BMI, both correlated (C3a negatively and adiponectin positively) with subcutaneous C3 and C3aR expression (p<0.05-0.001) or less).The obesity-induced down-regulation of complement C3 and C3aR which is specific to subcutaneous adipose tissue, coupled to the strong correlations with multiple anthropometric, plasma and adipokine variables support a potential role for complement in immunometabolism.
Background Although no receptor has yet been identified, changes in circulating levels of the adipokine designated as Omentin have been demonstrated in obesity and related comorbidities such as cardiovascular disease, insulin resistance, metabolic syndrome and chronic inflammation. Methods Changes in Omentin levels at 1 and 5 days and 6 and 12 months in response to biliopancreatic diversion with duodenal switch bariatric surgery were evaluated, specifically to investigate if changes preceded gain of insulin sensitivity. Results Pre-operative plasma Omentin was not different between men (n = 18) vs women (n = 48), or diabetic status but correlated with body mass index (BMI). Altogether, Omentin increased as early as 24-h post-surgery, with changes maintained up to 1-year. Fifty-nine percent of subjects increased Omentin >10% by 24-H following surgery (Omentin INC p < 0.0001), while 18% of subjects decreased (Omentin DEC p < 0.0001), with changes maintained throughout one-year. These two groups had comparable age, sex distribution, diabetes, BMI, waist circumference and fat mass, however Omentin DEC had elevated levels of cardiovascular risk markers; homocysteine (p = 0.019), NT-proBNP (p = 0.006) and total bilirubin (p = 0.0001) while red blood cell (RBC) count was lower (p = 0.0005) over the one-year period. Omentin levels at 1-DAY also correlated with immune parameters (white blood cell count, % neutrophil, % monocytes, % lymphocytes). Conclusion Omentin DEC at 1 day following surgery may be a marker of cardiovascular “at-risk” group before weight loss or insulin sensitivity restoration.
Objective . Obesity is associated with metabolic dysfunction with sex differences and chronic, low-grade inflammation. We proposed that hepatic expression of immune complement C3 related receptors (C3aR, C5aR, and C5L2) would be associated with pre- or postmenopausal status and metabolic profile in severely obese women. We hypothesized that C5L2/C5aR ratio, potentially influencing the ASP/C5L2 metabolic versus C5a/C5aR immune response, would predict metabolic profiles after weight loss surgery. Materials and Methods . Fasting plasma (hormone, lipid, and enzyme analysis) and liver biopsies (RT-PCR gene expression) were obtained from 91 women during surgery. Results . Hepatic C5L2 mRNA expression was elevated in pre- versus postmenopausal women (P<0.01) and correlated positively with circulating estradiol, estrone, ApoB, ApoA1, ApoA1/B, waist circumference, age, and LDL-C (allP<0.05). While plasma ASP was lower in pre- versus postmenopausal women (P<0.01), the hepatic C5L2/C5aR mRNA ratio was increased (P<0.001) and correlated positively with estrone (P<0.01) and estradiol (P<0.001) and negatively with circulating ApoB and liver enzymes ALT, AST, and GGT (allP<0.05). Over 12 months postoperatively, liver enzymes in low C5L2/C5aR mRNA ratio group remained higher (ALP and ALT,P<0.05, AST and GGT,P<0.0012-way-ANOVA). Conclusion . C5L2-C5aR association with other mediators including estrogens may contribute to hepatic metabolic and inflammatory function.
Background: Ketosis-prone diabetes (KPDM) is new-onset diabetic ketoacidosis without precipitating factors in non-type 1 diabetic patients; after management, some are withdrawn from exogenous insulin, although determining factors remain unclear.Methods: Twenty KPDM patients and twelve type 1 diabetic patients (T1DM), evaluated at baseline, 12 and 24 months with/without insulin maintenance underwent a standardized mixed-meal tolerance test (MMTT) for 2 h.Results: At baseline, triglyceride and C3 were higher during MMTT in KPDM vs. T1DM (p<0.0001) with no differences in non-esterified fatty acids (NEFA) while Acylation Stimulating Protein (ASP) tended to be higher. Within 12 months, 11 KPDM were withdrawn from insulin treatment (KPDM-ins), while 9 were maintained (KPDM+ins). NEFA was lower in KPDM-ins vs. KPDM+ins at baseline (p = 0.0006), 12 months (p<0.0001) and 24 months (p<0.0001) during MMTT. NEFA in KPDM-ins decreased over 30-120 minutes (p, 0.05), but not in KPDM+ins. Overall, C3 was higher in KPDM-ins vs KPDM+ins at 12 months (p = 0.0081) and 24 months (p = 0.0019), while ASP was lower at baseline (p = 0.0024) and 12 months (p = 0.0281), with a decrease in ASP/C3 ratio.Conclusions: Notwithstanding greater adiposity in KPDM-ins, greater NEFA decreases and lower ASP levels during MMTT suggest better insulin and ASP sensitivity in these patients.
Adipose tissue receptors C5aR and C5L2 and their heterodimerization/functionality and interaction with ligands C5a and acylation stimulating protein (ASP) have been evaluated in cell and rodent studies. Their contribution to obesity factors in humans remains unclear. We hypothesized that C5a receptors, classically required for host defense, are also associated with adiposity. Anthropometry and fasting blood parameters were measured in 136 women divided by body mass index (BMI): normal/overweight (≤30 kg/m(2); n = 34), obese I (≤45 kg/m(2); n = 33), obese II (≤51 kg/m(2); n = 33), and obese III (≤80 kg/m(2); n = 36). Subcutaneous and omental adipose tissue C5aR and C5L2 expression were analysed. C5L2 expression was comparable between subcutaneous and omental across all BMI groups. Plasma ASP and ASP/omental C5L2 expression increased with BMI (P < 0.001 and P < 0.01, resp.). While plasma C5a was unchanged, C5aR expression decreased with increasing BMI in subcutaneous and omental tissues (P < 0.01 and P < 0.05, resp.), with subcutaneous omental depots. Omental C5L2/C5aR ratio increased with BMI (P < 0.01) with correlations between C5L2/C5aR and waist circumference, HDL-C, and adiponectin. Tissue and BMI differences in receptors and ligands, particularly in omental, suggest relationship to metabolic disturbances and highlight adipose-immune interactions.
La Commission de Relations ouvrières, en accordant l'autorisation requise par la Loi des Différends entre les services publics et leurs salariés pour intenter des poursuites pénales, n'agit pas comme tribunal mais elle exerce un pouvoir qui lui est légalement accordé et pose un acte purement administratif qui ne peut être arrêté par un bref de prohibition. Cette autorisation ne participe pas à l'exercice d'un pouvoir judiciaire. S'il est possible de soulever la question de la constitutionnalité d'une loi au soutien d'une requête pour bref de prohibition, il faut tout de même que cette question se présente dans un cas où la loi autorite l'émission dun tel bref. M. le juge Rivard. L'article 5 de la Loi des Différends entre les services publics et leurs salariés (S.R.Q. 1941, ch. 169) qui interdit toute grève ou contre-grève en toute circonstance et l'article 7 de ladite loi qui impose une pénalité à quiconque déclare ou provoque une telle grève ou contre-grève ou y participe sont intra vires de la compétence de la Législature provinciale qui les a édictés. Vassard et un autre (Requérants) Appelants v. La Commission de Relations ouvrières de Québec, Intimée et Carier et Frères Ltée, Mise-en-cause et Le Procureur général de la Province, Intervenant. MM. les juges Casey, Rinfret, Taschereau, Owen et Rivard — No 7493 (C.S. 416,891) — Montréal, 10 mai 1962. Marc Lapointe et Denis Lévesque, pour les appelants; Laurent-E. Bélanger, c.r., pour l'intimée.
0303-7207/$ see front matter 2012 Elsevier Irelan http://dx.doi.org/10.1016/j.mce.2012.12.008 Abbreviations: Banp, Btg3 associated nuclear prot tor; C/EBP, CCAAT/enhancer binding protein; FA, fatt ylxanthine; IGF1, Insulin-like growth factor I; KC, kera KRB, Krebs’s Ringer Buffer; LYRM-1, LYR motif contain 2-thiazolyl)-3-(4-sulfophenyl); MCP1, monocyte c Myelocytomatosis oncogene; NEFA, non-esterified activity-modifying proteins. ⇑ Corresponding author. Address: Centre de Reche Cardiologie & Pneumologie de Québec, Université Lav Foy, Québec, QC, Canada G1V 4G5. Tel.: +1 418 656 4749. E-mail address: katherine.cianflone@criucpq.ulava Amylin is co-localized and co-secreted with insulin, however its direct effects on adipocytes are unexplored. In 3T3-L1 preadipocytes, amylin increased thymidine incorporation (174%; p < 0.05) and Myc mRNA expression (378%; p < 0.01). Amylin supplementation during differentiation enhanced triglyceride accumulation (272%; p < 0.001). In 3T3-L1 adipocytes, amylin increased fatty acid uptake (238%; p < 0.01) and further potentiated the effects of insulin (insulin 158%; p < 0.01, amylin + insulin 335%; p < 0.001 vs CTL, p < 0.001 vs insulin). By contrast, amylin inhibited glycerol release in 3T3-L1 adipocytes ( 50%; p < 0.05) and primary adipocytes ( 34%; p < 0.05). Amylin stimulated cytokine secretion (monocyte chemotactic protein-1 + 166%, keratinocyte-derived chemokine + 174%; both p < 0.05) and mRNA expression of PPARc (163%; p < 0.01), C/EBPb (121%, p < 0.05), DGAT1 (157%; p < 0.01), FABP4 (122%; p < 0.01), and CD36 (122%; p < 0.05). In human adipose tissue, mRNA expression of amylin receptor genes (CALCR and RAMP3) correlated with numerous lipid and insulin signaling genes, plasma glucose and HOMA. Altogether amylin directly stimulates fat cells, potentiates the effects of insulin and may influence insulin resistance. 2012 Elsevier Ireland Ltd. All rights reserved.
Acylation stimulating protein (ASP) is an adipokine derived from the immune complement system, which stimulates fat storage and is typically increased in obesity, type 2 diabetes, and cardiovascular disease. Using a diet-induced obesity (DIO) mouse model, the acute effects of ASP on energy metabolism and inflammatory processes in vivo were evaluated. We hypothesized that ASP would specifically exert proinflammatory effects. C57Bl/6 wild-type mice were put on a high-fat-high-sucrose diet for 12 weeks. Mice were then subjected to both glucose and insulin tolerance tests, each manipulation being preceded by recombinant ASP or vehicle (control) bolus injection. ASP supplementation increased whole-body glucose excursion, and this was accomplished with reduced concomitant insulin levels. However, ASP did not directly alter insulin sensitivity. ASP supplementation induced a proinflammatory phenotype, with higher levels of cytokines including IL-6 and TNF-α in plasma and in adipose tissue, liver, and skeletal muscle mRNA. Additionally, ASP increased M1 macrophage content of these tissues. ASP exerted a direct concentration-dependent role in the migration and M1 activation of cultured macrophages. Altogether, the in vivo and in vitro experiments demonstrate that ASP plays a role in both energy metabolism and inflammation, with paradoxical whole-body glucose-sensitizing yet proinflammatory effects.