lipid-a and Insulin-Resistance

Subclinical hypothyroidism (SCH) is encountered in 10-25% of women with PCOS. To date, it remains unclear whether this coexistence influences the severity of metabolic and hormonal profile of these patients. The purpose of our systematic review is to investigate this potential relation.. We systematically searched Medline, Scopus, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases together with reference lists from included studies. All prospective and retrospective observational cohort studies that investigated the impact of subclinical hypothyroidism on hormonal and metabolic parameters of PCOS patients were included. The methodological quality of studies was assessed with the Ottawa-Newcastle criteria. Statistical meta-analysis was performed with the RevMan 5.3 software.. Twelve studies were finally included in the present review, which enrolled 2341 PCOS patients. Among them, 577 had subclinical hypothyroidism, whereas the remaining 2077 were PCOS women with normal thyroid function. The presence of SCH significantly affected HDL (MD -3.92 mg/dL 95% CI: -6.56, -1.29) and triglycerides levels (26.91 mg/dL 95% CI: -3.79, 50.02). HOMA-IR was also affected (MD 0.82 95% CI: 0.15, 1.50). On the other hand, LDL, fasting glucose and 2-h OGTT were not influenced. Similarly, prolactin, FSH, LH, LH/FSH ratio and sex hormone-binding globulin remained unaffected.. Subclinical hypothyroidism does not influence the hormonal profile of women with PCOS. On the other hand, it results in mild metabolic abnormalities, which are not clinically important in a short-term setting.

Topics: Blood Glucose; Female; Follicle Stimulating Hormone; Humans; Hypothyroidism; Insulin Resistance; Lipid A; Luteinizing Hormone; Polycystic Ovary Syndrome; Severity of Illness Index; Sex Hormone-Binding Globulin

Several studies have implicated obesity-induced macrophage-adipocyte cross-talk in adipose tissue dysfunction and insulin resistance. However, the molecular cues involved in the cross-talk of macrophage and adipocyte causing insulin resistance are currently unknown. Here, we found that a lipid-induced monokine cyclophilin-A (CyPA) significantly attenuates adipocyte functions and insulin sensitivity. Targeted inhibition of CyPA in diet-induced obese zebrafish notably reduced adipose tissue inflammation and restored adipocyte function resulting in improvement of insulin sensitivity. Silencing of macrophage CyPA or pharmacological inhibition of CyPA by TMN355 effectively restored adipocytes' functions and insulin sensitivity. Interestingly, CyPA incubation markedly increased adipocyte inflammation along with an impairment of adipogenesis, however, mutation of its cognate receptor CD147 at P309A and G310A significantly waived CyPA's effect on adipocyte inflammation and its differentiation. Mechanistically, CyPA-CD147 interaction activates NF-κB signaling which promotes adipocyte inflammation by upregulating various pro-inflammatory cytokines gene expression and attenuates adipocyte differentiation by inhibiting PPARγ and C/EBPβ expression via LZTS2-mediated downregulation of β-catenin. Moreover, inhibition of CyPA or its receptor CD147 notably restored palmitate or CyPA-induced adipose tissue dysfunctions and insulin sensitivity. All these results indicate that obesity-induced macrophage-adipocyte cross-talk involving CyPA-CD147 could be a novel target for the management of insulin resistance and type 2 diabetes.

Topics: Adipose Tissue; Animals; Cyclophilin A; Cyclophilins; Diabetes Mellitus, Type 2; Inflammation; Insulin Resistance; Lipid A; Mice; Monokines; Obesity; Zebrafish

To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats.. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp.. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP.. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.

Topics: Animals; Body Weight; Diet, High-Fat; Glucose; Insulin Resistance; Lipid A; Lipids; Liver; Male; Obesity; Rats, Long-Evans; Rats, Wistar; Sulfonamides; Toll-Like Receptor 4

We aimed to evaluate the association between serum lipocalin-2 level and clinical and metabolic parameters in obese children.. The study included obese children with a body mass index (BMI) >95th percentile who presented to Kecioren Teaching and Research Hospital with the complaint of weight gain and healthy children with a BMI <85th percentile. The height and weight of the patients were measured for compartment of anthropometric data. Fasting blood glucose, insulin, lipid profile, and serum lipocalin-2 level were measured to evaluate the laboratory parameters.. The study included 33 obese and 34 healthy nonobese children. Comparison of data on the obese subjects with those of the healthy subjects shows differences in BMI, BMI-SDS, triglyceride, insulin, and homeostasis model assessment index-insulin resistance levels between the two groups were statistically significant (p < 0.05), whereas serum lipocalin-2 was not statistically significant (p >0.05). There was no statistically significant difference in serum lipocalin-2 levels when obese and control groups were reclassified as prepubertal and pubertal ( p >0.05).. In this study, we did not find any relationships among serum lipocalin-2 level, anthropometric parameters, or metabolic parameters. According to the results of this study, we do not suggest routine investigation of serum lipocalin-2 level in obese subjects for risk stratification of the obesity-related complications.

Topics: Acute-Phase Proteins; Adolescent; Blood Glucose; Body Mass Index; Child; Female; Homeostasis; Humans; Insulin Resistance; Lipid A; Lipocalin-2; Lipocalins; Male; Obesity; Pilot Projects; Proto-Oncogene Proteins; Risk Factors

The aim of this study was to elucidate the effect of fish-oil-derived monounsaturated fatty acids (MUFAs) containing large amounts of C20:1 and C22:1 isomers on metabolic disorders in mice. Male C57BL/6J mice were fed a 32% lard diet (control) or a 27% lard plus 5% saury-oil-derived MUFA diet for 6 weeks. Dietary MUFA improved insulin resistance and alleviated metabolic syndrome risk factors by reducing blood glucose and lipids. These favorable changes may be attributed to an improved adipocytokine profile. MUFA ingestion resulted in favorable changes in mRNA expression of genes involved in glucose/lipid metabolism (SCD-1, CPT1a, UCPs, and CS) as well as inflammation (MAC1, MMP3, and SAA3) and alterations in fatty acid composition. Our data suggest that marine MUFA improved glucose/lipid homeostasis and hindered the development of metabolic syndrome in obese mice.

Topics: Animals; Blood Glucose; Dietary Fats; Dietary Fats, Unsaturated; Fatty Acids, Monounsaturated; Fish Oils; Insulin Resistance; Lipid A; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity