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Eosinophils Reduce Chronic Inflammation in Adipose Tissue by Secreting Th2 Cytokines and Promoting M2 Macrophages Polarization

Obesity is now recognized as a low-grade, chronic inflammatory disease that is linked to a myriad of disorders including cardiovascular diseases, type 2 diabetes, and liver diseases. Recently it is found that eosinophils accelerate alternative activation macrophage (AAM) polarization by secreting Th2 type cytokines such as interleukin-4 and interleukin-13, thereby reducing metainflammation in adipose tissue. In this review, we focused on the role of eosinophils in regulating metabolic homeostasis and obesity.

FGF21 Is Associated with Acanthosis Nigricans in Obese Patients

Objective. We aimed to investigate the relationship between FGF21 and obesity-related acanthosis nigricans (AN). Methods. 40 obese patients without AN (OB group), 40 obese patients with AN (AN group), and 40 healthy volunteers (control group, CON) were included in this study. Weight, BMI, lipid profile, FFA, UA, and CRP were measured in all participants. Oral glucose tolerance tests (OGTT) were performed and serum glucose and plasma insulin were measured. Serum FGF21 was measured by ELISA. Results. Compared with OB group, AN group had higher levels of fasting insulin and homeostasis model of assessment for insulin resistance (HOMA-IR) (P < 0.05), but lower serum levels of blood glucose. The difference of FGF21 among three groups was significant and AN group showed the highest serum level of FGF21 (P < 0.05). Serum FGF21 was most positively correlated with fasting insulin and HOMA-IR. Multiple logistic analysis showed that FGF21 was the independent risk factor for AN (OR 4.550; 95% CI 1.054–19.635; P = 0.042). Conclusion. AN patients had more serious hyperinsulinemia but better serum levels of blood glucose than OB. Increased FGF21 is associated with AN in obese patients and may be considered as compensatory response to the decreased insulin sensitivity.

Serum Irisin Level is Higher and Related with Insulin in Acanthosis Nigricans-related Obesity

OBJECTIVE Acanthosis nigricans (AN) is proved to be a skin phenotype of hyperinsulinemia especially in obese patients. Irisin is a new myokine which plays an important role in metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes. The role of irisin in the development of AN-related obesity is not yet understood. In this study, we aimed to investigate the relationship between irisin and AN-related obesity. Patients & Measurements: 30 obese patients without AN (OB group), 30 obese patients with AN (AN group), and 20 age-matched healthy volunteers (control group, CON) were included in this study. Weight, BMI, lipid profile, FFA, UA, and CRP were measured in all participants. Oral Glucose Tolerance tests (OGTT) were performed and serum glucose and plasma insulin were measured at 0, 30, 60,120 and 180 min. The AUC (area under curve) of glucose and insulin was calculated. Serum irisin was measured by ELISA. RESULTS Hyperinsulinemia is found in both AN and OB groups. The AN group had higher levels of insulin but better blood glucose tolerance and insulin response. The difference in irisin levels between the 3 groups was statistically significant, with the AN group showing the highest serum level of irisin. Serum irisin levels were positively correlated with BMI, and fasting insulin. CONCLUSION AN is a state of hyperinsulinmia and has better insulin response and glucose tolerance compared to obese patients without AN. Serum irisin may be a protective factor against impaired beta cell function in obesity with AN.

The Associations of Serum Uric Acid with Obesity-Related Acanthosis nigricans and Related Metabolic Indices

Objective. Recent studies have shown that hyperuricemia (HUA) is associated with hypertension, dyslipidemia, insulin resistance, and metabolic syndrome (MetS). We aimed to examine the relationship of serum UA with Acanthosis nigricans (AN) and related metabolic indices in obese patients. Methods. A cross-sectional study with 411 obese patients recruited from our department was analyzed in this study. Weight, body mass index (BMI), UA, lipid profile, liver function, and renal function were measured in all participants. Oral glucose tolerance tests were performed, and serum glucose, insulin, and C peptide were measured at 0, 30, 60, 120, and 180 min. Results. AN group had higher serum UA levels than OB group. Circulating UA levels were associated with BMI, dyslipidemia, hypertension, IR, and AN. In logistic regression analyses (multivariable‐adjusted), a high serum UA level was associated with high odds ratios (ORs) (95% confidence interval [CI]) for AN in females (ORs = 3.00 and 95% CI [1.02–8.84]) and males (ORs = 6.07 and 95% CI [2.16–17.06]) in the highest quartile (Q4) of serum UA. Conclusions. Serum UA levels were positively associated with multiple metabolic abnormalities including obesity, hypertension, hyperglycemia, hyperlipidemia, and AN and may be an important risk factor in the development of AN; further evidences in vitro and in vivo are needed to investigate the direct or indirect relationship.

Clinical Evaluation of Various Thyroid Hormones on Thyroid Function

To clarify the clinical value of serums total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) and provide a more eligible and economic strategy to assess thyroid function. A total of 2,673 participants (500 patients with hyperthyroidism, 500 patients with hypothyroidism, and 1,673 healthy people) were involved in our study. Serums TT3, TT4, FT3, and FT4 and thyrotropin (TSH) were measured with VIDAS fluorescent enzyme immunoassay. The Pearson correlation between TT3, TT4, FT3, and FT4 and TSH was determined to identify the most important indicator for thyroid function besides TSH. The correlation of TT4, and FT4 with TSH was statistically significant in healthy individuals (P < 0.01), and the R-values were −0.065 and −0.152, respectively. The correlation of TT4, FT4, TT3, and FT3 with TSH was statistically significant in patients with hyperthyroidism, and the R-values were −0.241, −0.225, −0.195, and −0.176, respectively. The correlation of TT4, FT4, TT3, and FT3 with TSH was statistically significant in patients with hypothyroidism, and the R-values were −0.322, −0.262, −0.179, and −0.136, respectively. In our opinion, TSH and FT4 are the most valuable indicators in assessing thyroid function in a healthy population, and TSH and TT4 are the most meaningful in hyperthyroidism and hypothyroidism.

ATP Synthase β-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level

HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase β-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase β-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase β-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of β-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL-HDL uptake in primary hepatocytes. In response to hepatic overexpression of β-chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase β-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C.

Activated central galanin type 1 receptor alleviated insulin resistance in diabetic rat muscle.

Evidence indicates that central galanin is involved in regulation of insulin resistance in animals. This study investigates whether type 1 galanin receptor (GAL1) in the brain mediates the ameliorative effect of galanin on insulin resistance in skeletal muscles of type 2 diabetic rats. Rats were intracerebroventricularly (i.c.v.) injected with galanin(1–13)‐bradykinin(2–9) amide (M617), a GAL1 agonist, and/or Akti‐1/2, an Akt inhibitor, via caudal veins once per day for 10 days. Insulin resistance in muscle tissues was evaluated by glucose tolerance and 2‐[N‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino]‐2‐deoxyglucose (2‐NBDG) tests, peroxisome proliferator‐activated receptor‐γ (PPARγ), glucose transporter 4 (GLUT4) mRNA expression levels, Akt phosphorylation, and GLUT4 and vesicle‐associated membrane protein 2 (VAMP2) concentration at plasma membranes in muscle cells. The results show that i.c.v. treatment with M617 increased glucose tolerance, 2‐NBDG uptake, PPARγ levels, Akt phosphorylation, GLUT4 protein, and GLUT4 mRNA expression levels as well as GLUT4 and VAMP2 concentration at plasma membranes. All increases may be blocked by pretreatment with Akti‐1/2. These results suggest that activated central GAL1 may trigger the Akt signaling pathway to alleviate insulin resistance in muscle cells. Therefore, the impact of galanin on insulin resistance is mediated mainly by GAL1 in the brain, and the GAL1 agonist may be taken as a potential antidiabetic agent for treatment of type 2 diabetes mellitus.

HbA1c as a Screening tool for Ketosis in Patients with Type 2 Diabetes Mellitus.

Ketosis in patients with type 2 diabetes mellitus (T2DM) is overlooked due to atypical symptoms. The objective of this study is to evaluate the value of hemoglobin A1c (HbA1c) as a screening tool for ketosis in T2DM patients. This retrospective study consisted of 253 T2DM patients with ketosis at Shanghai 10th People’s Hospital during a period from January 1, 2011 to June 30, 2015. A control group consisted of 221 T2DM patients without ketosis randomly selected from inpatients during the same period. Receiver operating characteristic curve (ROC) analysis was used to examine the sensitivity and specificity of HbA1c as an indicator for ketosis. Higher HbA1c levels were correlated with ketosis. In patients with newly diagnosed T2DM, the area under the curve (AUC) was 0.832, with 95% confidence interval (CI) 0.754–0.911. The optimal threshold was 10.1% (87 mmol/mol). In patients with previously diagnosed T2DM, the AUC was 0.811 (95% CI: 0.767–0.856), with an optimal threshold of 8.6% (70 mmol/mol). HbA1c is a potential screening tool for ketosis in patients with T2DM. Ketosis is much more likely with HbA1c values at ≥10.1% in patients with newly diagnosed T2DM and HbA1c values at ≥8.6% in patients with previously diagnosed T2DM.

Preventative Sleeve Gastrectomy Contributes to Maintaining β Cell Function in db/db Diabetic Mouse.

BackgroundWe used the leptin-receptor (LPR)-deficient mice model (db/db), a spontaneous model of type 2 diabetes with early β cell dysfunction to determine whether a preventative sleeve gastrectomy (SG) is an effective technique for the treatment of β cell failure.MethodsThe animals operated at an early stage of life, prior to metabolic alterations, were used to study the molecular mechanisms of β cell function improvement after a SG.Resultsβ cell function was significantly increased, and islet morphology remained normal, after the SG. The expression of Glut2, Pdx1, MafA, and Nkx6.1 were significantly increased after the SG. The expression of GLP-1 in the colonic tissue, as well as GLP-1R and PKC in islets, was significantly increased after the SG.Conclusionsβ cell dysfunction can be ameliorated by a preventative SG for db/db mice. Maintaining the GLP-1 pathway and key transcript factor (TF) activation contributes to the improvement of β cell function after a preventative SG.