Insulin Resistance In Obesity Research Articles

Deletion of CD44 promotes adipogenesis by regulating PPARγ and cell cycle-related pathways.

CD44, a cell surface adhesion receptor and stem cell biomarker, is recently implicated in chronic metabolic diseases. Ablation of CD44 ameliorates adipose tissue inflammation and insulin resistance in obesity. Here, we investigated cell type-specific CD44 expression in human and mouse adipose tissue and further studied how CD44 in preadipocytes regulates adipocyte function. Using Crispr Cas9-mdediated gene deletion and lentivirus-mediated gene re-expression, we discovered that deletion of CD44 promotes adipocyte differentiation and adipogenesis, whereas re-expression of CD44 abolishes this effect and decreases insulin responsiveness and adiponectin secretion in 3T3-L1 cells. Mechanistically, CD44 does so via suppressing Pparg expression. Using quantitative proteomics analysis, we further discovered that cell cycle-regulated pathways were mostly decreased by deletion of CD44. Indeed, re-expression of CD44 moderately restored expression of proteins involved in all phases of the cell cycle. These data were further supported by increased preadipocyte proliferation rates in CD44-deficient cells and re-expression of CD44 diminished this effect. Our data suggest that CD44 plays a crucial role in regulating adipogenesis and adipocyte function possibly through regulating PPARγ and cell cycle-related pathways. This study provides evidence for the first time that CD44 expressed in preadipocytes plays key roles in regulating adipocyte function outside immune cells where CD44 is primarily expressed. Therefore, targeting CD44 in (pre)adipocytes may provide therapeutic potential to treat obesity-associated metabolic complications.

Relationship between the efficacy of sulfonylurea therapy and structural variants of the ABCC8 (rs757110) and KCNJ11 (rs5219) genes in patients with type 2 diabetes mellitus with different phenotypes

Recently, a large number of studies have been conducted to investigate the variability of response in the treatment of diabetes mellitus (T2DM), which make personalized medicine possible. However, the available data are insufficient to decide on the choice of sugar-lowering drugs in T2DM. The search for phenotypic and clinical factors of pharmacogenetic response to therapy continues. Aim of the study was to investigate the relationship between the effectiveness of sulfonylurea therapy and structural variants of the ABCC8 (rs757110) and KCNJ11 (rs5219) genes in T2DM patients with clinical phenotypes. Material and methods. A cross-sectional clinical and pharmacogenetic study of 1271 patients with T2DM receiving sulfonylurea monotherapy (SU) or in combination with metformin and divided into three clinical phenotypes: with insulin deficiency (insulinopenic phenotype), with obesity and moderate insulin resistance (classical phenotype) and with severe insulin resistance (insulin-resistant phenotype) was performed. A glycated hemoglobin content of less than 7% was considered as a good response to SU therapy. Results. Patients with a good response to SU therapy with a classic phenotype had a longer duration of diabetes compared to patients with absence of good response (5.68 ± 5.22 vs 9.12 ± 6.10 years, respectively, p < 0.001) and a later age at diagnosis of T2DM (54.05 ± 7.18 vs 49.37 ± 7.65 years, respectively, p < 0.001); patients with an insulin-resistant phenotype had T2DM established at an older age (54.35 ± 7.91 vs 50.10 ± 7.51 years, respectively, p = 0.001). Logistic regression analysis did not reveal a statistically significant association of the genotype of the structural variant of the ABCC8 gene (rs757110) with the effectiveness of SU in clinical phenotypes. The T/T genotype of the KCNJ11 gene (rs5219) was associated with a better response to SU therapy only in the group of T2DM patients with the classic phenotype (odds ratio 1.85, 95% confidence interval 1.05–3.25, p = 0.041). Conclusions. In patients with type 2 diabetes, predictors of a good response to SU with a classic phenotype were a later age of T2DM diagnosis, a shorter duration of diabetes, and the presence of the T/T genotype of the structural variant of the KCNJ11 gene (rs5219); with an insulin-resistant phenotype, a later age of T2DM diagnosis; with the insulinopenic phenotype no clinical and genetic predictors of the SU effectiveness were identified.

Mechanistic insights into the role of USP14 in adipose tissue macrophage recruitment and insulin resistance in obesity

Diet-induced obesity can cause metabolic syndromes. The critical link in disease progression is adipose tissue macrophage (ATM) recruitment, which drives low-level inflammation, triggering adipocyte dysfunction. It is unclear whether ubiquitin-specific proteinase 14 (USP14) affects metabolic disorders by mediating adipose tissue inflammation. In the present study, we showed that USP14 is highly expressed in ATMs of obese human patients and diet-induced obese mice. Mouse USP14 overexpression aggravated obesity-related insulin resistance by increasing the levels of pro-inflammatory ATMs, leading to adipose tissue inflammation, excessive lipid accumulation, and hepatic steatosis. In contrast, USP14 knockdown in adipose tissues alleviated the phenotypes induced by a high-fat diet. Co-culture experiments showed that USP14 deficiency in macrophages led to decreased adipocyte lipid deposition and enhanced insulin sensitivity, suggesting that USP14 plays an important role in ATMs. Mechanistically, USP14 interacted with TNF receptor-associated 6, preventing K48-linked ubiquitination as well as proteasome degradation, leading to increased pro-inflammatory polarization of macrophages. In contrast, the pharmacological inhibition of USP14 significantly ameliorated diet-induced hyperlipidemia and insulin resistance in mice. Our results demonstrated that macrophage USP14 restriction constitutes a key constraint on the pro-inflammatory M1 phenotype, thereby inhibiting obesity-related metabolic diseases.

Correlation of Leptin in Patients With Type 2 Diabetes Mellitus.

The exponential increase in diabetes mellitus (DM) poses serious public health concerns. In this review, we focus on the role of leptin in type 2 DM. The peripheral actions of leptin consist of upregulating proinflammatory cytokines which play an important role in the pathogenesis of type 2 DM and insulin resistance. Moreover, leptin is known to inhibit insulin secretion and plays a significant role in insulin resistance in obesity and type 2 DM. A literature search was conducted on Medline, Cochrane, Embase, and Google Scholar for relevant articles published until December 2023. The following search strings and Medical Subject Headings (MeSH terms) were used: "Diabetes Mellitus," "Leptin," "NPY," and "Biomarker." This article aims to discuss the physiology of leptin in type 2 DM, its glucoregulatory actions, its relationship with appetite, the impact that various lifestyle modifications can have on leptin levels, and, finally, explore leptin as a potential target for various treatment strategies.

Effects of Saikosaponin-A on Insulin Resistance in Obesity: Computational and Animal Experimental Study.

Obesity is known to be associated with increased inflammation and dysregulated autophagy, both of which contribute to insulin resistance. Saikosaponin-A (SSA) has been reported to exhibit anti-inflammatory and lipid-lowering properties. In this research, we employed a combination of computational modeling and animal experiments to explore the effects of SSA. Male C57BL/6 mice were categorized into four groups: normal diet, high-fat diet (HFD), HFD + atorvastatin 10 mg/kg, and HFD + SSA 10 mg/kg. We conducted oral glucose and fat tolerance tests to assess metabolic parameters and histological changes. Furthermore, we evaluated the population of Kupffer cells (KCs) and examined gene expressions related to inflammation and autophagy. Computational analysis revealed that SSA displayed high binding affinity to tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, fibroblast growth factor 21 (FGF21), and autophagy-related 7 (ATG7). Animal study demonstrated that SSA administration improved fasting and postprandial glucose levels, homeostatic model assessment of insulin resistance (HOMA-IR) index, as well as triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol (LDL-C)-cholesterol, and high-density lipoprotein cholesterol (HDL-C)-cholesterol levels in HFD-fed mice. Moreover, SSA significantly reduced liver weight and fat accumulation, while inhibiting the infiltration and M1 activation of KCs. At the mRNA level, SSA downregulated TNF-α and NF-κB expression, while upregulating FGF21 and ATG7 expression. In conclusion, our study suggests that SSA may serve as a therapeutic agent for addressing the metabolic complications associated with obesity. This potential therapeutic effect is attributed to the suppression of inflammatory cytokines and the upregulation of FGF21 and ATG7.

Metabolic dysfunction-associated steatotic liver disease-related hepatic fibrosis increases risk of insulin resistance, type 2 diabetes, and chronic kidney disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) (previously called nonalcoholic fatty liver disease, NAFLD) is associated with cardiometabolic risk factors and chronic kidney disease (CKD). However, evidence is lacking regarding whether the severity of fibrosis is affected by these risk factors and diseases and to what degree. We aimed to determine the correlation between these factors and vibration-controlled transient elastography-determined liver stiffness measurements (LSMs) and controlled attenuation parameter (CAP) values in a sample of the US population. Data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey were pooled. The association between LSM and cardiometabolic risk factors and CKD was assessed using generalized linear or logistic regression analyses. In multivariate regression analyses, CAP and BMI were adjusted as confounders. Of 3647 participants, 2079 (57.1%) had NAFLD/MASLD [weighted prevalence 54.8%; 95% confidence interval (CI) 51.8-57.9%]; the weighted prevalence of significant fibrosis (LSM ≥ 7.9 kPa) was 9.7% (95% CI 8.2-11.3%). Log LSM was associated with higher levels of homeostatic model assessment of insulin resistance ( β = 2.19; P = 0.017), hepatic steatosis (CAP > 248 dB/m) [odds ratio (OR) 3.66; 95% CI 2.22-6.02], type 2 diabetes (OR 2.69; 95% CI 1.72-4.20), and CKD (OR 1.70; 95% CI 1.24-2.34). These correlations did not change notably after adjustments were made for waist circumference, CAP, and BMI. LSM and CAP, although influenced by waist circumference and BMI, are good indicators of hepatic fibrosis and steatosis. LSM is associated with insulin resistance, diabetes, and CKD independent of hepatic steatosis and obesity.

Syrah Grape Polyphenol Extracts Protect Human Skeletal Muscle Cells from Oxidative and Metabolic Stress Induced by Excess of Palmitic Acid: Effect of Skin/Seed Ripening Stage.

Metabolic skeletal muscle (SM) dysfunction, triggered by increased oxidative stress and mitochondrial impairment, is a pivotal contributor to obesity-associated insulin resistance (IR). Addressing obesity and SM IR demands substantial lifestyle changes including regular exercise and dietary adjustments that are difficult to follow over time. This prompted exploration of alternative approaches. Grape polyphenols (GPPs) have demonstrated a positive impact on metabolism, although few studies have focused on SM. Since grape polyphenolic content and composition depend on tissue and ripening, we explored the antioxidant potential of GPPs from skin (Sk) and seeds (Sd) extracted before veraison (Bv) and at mature (M) stages, on palmitate-induced IR in primary human SM cells. Despite their important difference in polyphenol (PP) content: Sd-BvPP > Sd-MPP/Sk-BvPP > Sk-MPP, all extracts reduced lipid peroxidation by 44-60%, up-regulated the heme-oxygenase 1 protein level by 75-132% and mitochondrial activity by 47-68%. Contrary to the other extracts, which improved insulin response by 50%, Sd-BvPP did not. Our findings suggest that compounds other than stilbenoids or anthocyanin-type molecules, present only in grape Sk, could play an active role in regulating SM oxidative and metabolic stress and insulin sensitivity, paving the way for further exploration of novel bioactive compounds.

History and future perspectives of adipose tissue macrophage biology.

Macrophages contribute to adipose tissue homeostasis; however, they are also thought to be responsible for insulin resistance in obesity. Macrophages, which were oversimplified in past methodologies, have become rather difficult to understand comprehensively as recent developments in research methodology have revealed their diversity. This review highlights recent studies on adipose tissue macrophages, identifies controversial issues that need to be resolved and proposes a scenario for further development of adipose tissue macrophage biology.

The mitochondrial quality control system: a new target for exercise therapeutic intervention in the treatment of brain insulin resistance-induced neurodegeneration in obesity.

Obesity is a major global health concern because of its strong association with metabolic and neurodegenerative diseases such as diabetes, dementia, and Alzheimer's disease. Unfortunately, brain insulin resistance in obesity is likely to lead to neuroplasticity deficits. Since the evidence shows that insulin resistance in brain regions abundant in insulin receptors significantly alters mitochondrial efficiency and function, strategies targeting the mitochondrial quality control system may be of therapeutic and practical value in obesity-induced cognitive decline. Exercise is considered as a powerful stimulant of mitochondria that improves insulin sensitivity and enhances neuroplasticity. It has great potential as a non-pharmacological intervention against the onset and progression of obesity associated neurodegeneration. Here, we integrate the current knowledge of the mechanisms of neurodegenration in obesity and focus on brain insulin resistance to explain the relationship between the impairment of neuronal plasticity and mitochondrial dysfunction. This knowledge was synthesised to explore the exercise paradigm as a feasible intervention for obese neurodegenration in terms of improving brain insulin signals and regulating the mitochondrial quality control system.

Insulin resistance and metabolic diseases - a review

Introduction: This review paper aims to discuss the effects of insulin resistance, and its association with various metabolic diseases. Insulin resistance (IR), characterized by diminished tissue responsiveness to physiological insulin levels, is a key component in various metabolic diseases, including type 2 diabetes, cardiovascular disorders (CVDs), obesity, and non-alcoholic fatty liver disease (NAFLD).
 State of knowledge The consequences of IR are profound; in type 2 diabetes, it hinders glucose utilization by muscle cells, leading to hyperglycemia, muscle damage, and loss of mass and strength. IR also plays a central role in NAFLD, promoting lipid accumulation, hepatic inflammation, fibrosis, and cell death.
 Materials and methods: A review of chosen literature in the PubMed and Google Scholar databases was conducted, using the following key words: „Insulin resistane”, „Insulin resistance in obesity”, „Obesity”, „Insulin resistance NAFLD”, „Diebetes”, „Insulin resistance CVD”
 Summary: The consequences of insulin resistance are far-reaching. In the context of type 2 diabetes, it impedes glucose utilization by muscle cells, resulting in hyperglycemia and subsequent muscle cell damage, contributing to loss of mass and strength. Insulin resistance is also a central player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), fostering lipid accumulation, hepatic inflammation, and, ultimately, fibrosis and cell death.
 Conclusions: In conclusion, understanding insulin resistance is paramount in addressing the rising prevalence of metabolic diseases globally Controlling insulin resistance emerges as a crucial aspect of managing these metabolic disorders and their complications. Further research into the mechanisms of IR formation and effective intervention strategies is imperative for improving public health outcomes.

Gastric Submucosal Fat Accumulation Is Associated with Insulin Resistance in Patients with Obesity

PurposeEctopic fat accumulation plays a significant role in obesity-related metabolic dysfunction, and few studies have reported an association between ectopic gastric fat and metabolic risk factors. We aim to fulfill this need by assessing the degree of gastric submucosal fat accumulation in pathologic sections of 190 sleeve gastrectomy specimens.MethodsStudy patients were divided into two groups (D1 and D2) based on whether fat accumulation exceeded 1/3 of the submucosa of the stomach. Demographic and metabolic risk factors were compared between the two groups. Metabolic risk variables that might be associated with the degree of fat accumulation were screened in the original cohort. After balancing for possible confounders, the robustness of the correlations was assessed using binary and conditional logistic regression analyses.ResultsAll study patients had fat accumulation in the submucosa of the stomach. C-reactive protein (CRP), body mass index (BMI), visceral fat area (VFA), and insulin resistance (IR) were higher in the D2 group than in the D1 group in the original cohort (P < 0.05). Logistic regression analysis showed that BMI and IR may be associated with increased fat accumulation. After balancing variables other than obesity indicators and IR using propensity score matching, BMI and IR remained significantly different between the two groups (P < 0.05). Further analysis of the matched cohort using two logistic regression analyses showed that IR was an independent risk factor for increased fat accumulation.ConclusionThis study indicated that gastric submucosal fat accumulation was prevalent in patients with obesity and was associated with IR.Graphical

Cyclosorus Terminans Extract Alleviates Neuroinflammation in Insulin Resistant Rats.

High-fat diet consumption for an extended period causes obesity, systemic metabolic disturbance, and brain insulin resistance, resulting in neuroinflammation. Although the beneficial effect of Cyclosorus terminans extract on obesity-related insulin resistance has been demonstrated, little is known about how it affects neuroinflammation and brain insulin resistance in obese rats. Male Wistar rats were given either a normal diet (ND, n = 6) or a high-fat diet (HFD, n = 24) for a total of 14 weeks. At the beginning of the week, 13 rats in the ND group were given vehicle orally for 2 weeks, while rats on HFD diets were randomized to one of four groups and given either vehicle, 100 mg/kg/day of Cyclosorus terminans extract, 200 mg/kg/day of Cyclosorus terminans extract, or 20 mg/kg/day of pioglitazone orally for 2 weeks. After the experimental period, blood and brain samples were taken to assess metabolic and brain parameters. HFD-fed rats had obesity, systemic and brain insulin resistance, brain inflammation, microglial and astrocyte hyperactivity, and brain necroptosis. Treatment with 200 mg/kg/day of Cyclosorus terminans extract and pioglitazone equally attenuated obesity, insulin resistance, brain insulin dysfunction, and neuroinflammation in insulin resistant rats. Our findings suggest that Cyclosorus terminans extract may hold promise as a therapeutic agent for insulin resistance and neuroinflammation in obese conditions.

Additive interactions between obesity and insulin resistance on hypertension in a Chinese rural population

BackgroundAdiposity and insulin resistance (IR) are closely associated with hypertension; however, the role of interactions between obesity phenotypes and IR in hypertension is unclear. This study aimed to evaluate the interactions of body mass index (BMI), waist circumference (WC), and body fat percentage (BF%) with IR on hypertension risk.MethodsWe analyzed data from 4888 participants (mean age 57 years, 41.2% men) in the China Northwest Natural Population Cohort, Ningxia Project. BMI, WC, and BF% were determined using bioelectrical impedance analysis devices. IR was estimated using a homeostasis model assessment index (HOMA-IR). Multivariable-adjusted logistic regression was used to evaluate the association between HOMA-IR and hypertension risk. We calculated the relative excess risk and attributable proportion with their 95% confidence intervals (CIs) to assess whether adiposity phenotypes modified the effect of HOMA-IR on hypertension risk.ResultsThe crude prevalence of hypertension was 52.2%. The multivariable-adjusted odds ratio of HOMA-IR was 1.80 (95% CI: 1.23–2.65) for the risk of hypertension in the highest versus the lowest quartiles, but this association became marginal in models further adjusting for BMI, WC, and BF% (P for trend = 0.056). Relative excess risk and attributable proportion for interaction between high HOMA-IR and high BF% were 0.32 (0.04–0.59) and 0.33 (0.06–0.60), respectively. Additionally, high truncal and leg BF% and high HOMA-IR accounted for the hypertension risk in women, but not in men. We did not observe any significant interactions between BMI or WC and HOMA-IR on hypertension.ConclusionBF% modified the association between IR and increased risk of hypertension in women with high truncal and leg BF%, but not in men.

A single session of strength training changed plasma levels of resistin, but not leptin in overweight and obese men

Obesity has a complex multifactorial etiology and is characterized by excessive accumulation of adipose tissue. Visceral adipose tissue has deleterious effects on health because it secretes large amounts of inflammatory cytokines. Nutritional calorie restriction associated with strength training may be useful in managing chronic systemic inflammation. This study aimed to evaluate the acute effect of a single strength-training session on plasma adipokine levels in sedentary, overweight, and obese young men. This study included twelve men (Age: [34.95 ± 9.77] years; Height: [174.16 ± 3.66] centimeter [cm]; Weight: [97.83 ± 12.87] kilogram (kg); body mass index [BMI]: [32.30 ± 4.51] kg/m2), who performed a single strength training session. The strength training protocol consisted of 4 sets of 12 repetitions in the following six exercises, 45° leg press, bench press, leg extension, machine row, leg curl, and shoulder press. Blood samples were collected before, immediately after, and 1-h subsequent after strength training. The plasma levels of resistin and leptin were measured. A significant decrease in resistin levels were found 1 h after the strength training session if compared to levels before the training session (pre-[before] [2390 ± 1199] picograms per milliliter [pg/mL] vs post-1 h [1-h subsequent] [1523 ± 798],6 pg/mL, p = 0.002 8). The plasma leptin levels did not differ at any time point. In conclusion, a very well controlled single session of strength training significantly decreased the plasma levels of resistin without altering the concentration of leptin in overweight and obese individuals. This effect, at least in part, supports the benefits of exercise by reducing the low grade inflammation and insulin resistance in obesity.

Role of miR‐802 in brain insulin signaling and its impact on Down syndrome

AbstractBackgroundDown syndrome (DS) individuals are characterized by a variety of pathological phenotypes that manifest with wide variability in the different tissues. At the level of the central nervous system, the accelerated aging phenotype is associated with the risk to develop Alzheimer‐like dementia. A central aspect of neurodegeneration is the close association between metabolic disorders and cognitive decline. Multiple studies have suggested a link between metabolic disorder and microRNAs (miR), small non‐coding RNAs acting as post‐transcriptional regulators of a plethora of genes. Among triplicated miRNAs on chromosome 21, we focus on miR‐802 because recent studies demonstrated its association with development on insulin resistance in obesity and diabetes. Considering these findings and based on the “gene dosage hypothesis” of DS, the goal of the study is to decipher how miR‐802 may contribute to aberrant insulin signaling (IS) and, in parallel to the risk to develop dementia early in life in DS. MethodThe miR‐802 expression, protein levels and activation state of main components of the IS were evaluated (i) in the brain of autoptic cases from DS, DSAD and age‐matched controls and (ii) in the brain of euploid and Ts65Dn mice (a model of DS). Further, using bioinformatic tools we identified miR‐802 predicted target genes that are involved in the IS (PTEN and GSK‐3β).ResultThe IS alterations worsen in the transition from DS to DS/AD and similar findings were collected inTs65Dn mice where IS dysregulation persists with aging where neurodegeneration becomes significant. Intriguingly, these latter changes were driven by the over‐expression of miR‐802, which negatively regulates PTEN and GSK‐3β mRNA in the brain.ConclusionIn this picture, the identification of specific targets modulated by miR‐802 and involved in IS pathway, will provide molecular basis to develop novel therapeutic strategies to prevent/delay the onset of brain insulin resistance in DS.

Assessing insulin resistance in obesity: An unresolved challenge

Assessing insulin resistance in obesity: An unresolved challenge

Gymnema sylvestre extract improves PCOS by altering the YAP1 protein in the mouse ovary via mitochondrial changes

BackgroundGymnema sylvestre (Retz.) R.Br. ex Sm. is a medicinal herb used in Ayurvedic medicine to treat diabetes. Through promoting obesity and lowering insulin resistance, anti-diabetic herbs may be more effective in treating polycystic ovarian syndrome (PCOS). Recently, YES‐associated protein-1 gene (YAP1) has been reported to be a new susceptibility gene for PCOS in clinical studies. Hence, we evaluated the effects of hydroalcoholic G. sylvestre extract on regulating the YAP1 protein in PCOS mice injected with dehydroepiandrosterone (DHEA) by examining mitochondrial alterations in the ovary. Materials and methodsThe DHEA-induced PCOS female C57BL6/J mice were treated with three doses of G. sylvestre and standard drug metformin. Study parameters include body weight gain, estrus cyclicity, glucose tolerance testing, serum hormone levels, lipid profiles, liver enzymes, and inflammatory cytokines. Electron microscopy, histological, and immuno-histochemical (IHC) analyses were used to determine the morphological changes of the ovary. IHC analysis was used to assess the expression of the YAP1 protein. ResultsAs compared with the control group, the G. sylvestre-treated groups showed decreased obesity, estrus irregularity, improved glucose metabolism, reduced AST and ALT values, hormonal abnormalities, and inflammatory cytokines (IL-6, IL-17, IL-23, TNF-α). Interestingly, metformin and G. sylvestre therapy reduced YAP1-positive cells in the ovary of DHEA-induced PCOS mice. ConclusionThese findings suggest that a higher concentration of G. sylvestre extract at 500 mg/kg improved mitochondrial architecture in the PCOS ovary via modulating the key pathogenic protein of PCOS, YAP1.

GIPR Agonism Enhances TZD-Induced Insulin Sensitivity in Obese IR Mice.

Recent studies have found that GIPR agonism can enhance the metabolic efficacy of GLP-1R agonist treatment by promoting both weight-dependent and -independent improvements on systemic insulin sensitivity. These findings have prompted new investigations aimed at better understanding the broad metabolic benefit of GIPR activation. Herein, we determined whether GIPR agonism favorably influenced the pharmacologic efficacy of the insulin sensitizing thiazolidinedione, rosiglitazone in obese insulin resistant (IR) mice. Genetic and pharmacological approaches were employed to examine the role of GIPR signaling on rosiglitazone-induced weight gain, hyperphagia, and glycemic control. RNA-sequencing was conducted to uncover potential mechanisms by which GIPR activation influences energy balance and insulin sensitivity. In line with previous findings, treatment with rosiglitazone induced the mRNA expression of the GIPR in white and brown fat. However, obese GIPR null mice dosed with rosiglitazone displayed equivalent weight gain to that of wild-type (WT) animals. Strikingly, chronic treatment of obese IR WT animals with a long-acting GIPR agonist (LAGIPRA) prevented rosiglitazone-induced weight-gain and hyperphagia, and it enhanced the insulin-sensitivity effect of this thiazolidinedione. The systemic insulin sensitization was accompanied by increased glucose disposal in brown adipose tissue (BAT), which was underlined by the recruitment of metabolic and thermogenic genes. These findings suggest that GIPR agonism can counter the negative consequences of rosiglitazone treatment on body weight and adiposity, while at the same time improving its insulin sensitizing efficacy.

TG/HDL-C Ratio for Predicting Insulin Resistance in Obese Children from Beijing, China

Background:: International studies have found that the blood triglycerides to highdensity lipoproteins (TG/HDL-C) ratio predicted insulin resistance in children with overweight and obesity. However, there is a lack of such reports on children from China. Objective:: The objective of this study is to explore the ability of the TG/HDL-C ratio as a blood biomarker for insulin resistance (IR) in obese children in Beijing. Methods:: We evaluated 262 children with obesity from our paediatric outpatient clinic in a cross-sectional study. Detailed medical histories of all children were ascertained, as were clinical examination and laboratory test results, including blood lipids, fasting glucose, insulin, and glycated haemoglobin. We divided them into age groups of 6-9 and 10-13.5 years and then into IR and non-IR groups based on the homeostatic model assessment for IR (HOMA-IR). Analysis was accomplished with SPSS software (version 22.0). Results:: The TG/HDL-C ratio was higher in children with IR in the 6-9 and 10-13.5-year age groups (p &lt; 0.001). Univariate and multivariate analyses displayed that the TG/HDL-C ratio and HOMA-IR were correlated in the 6-9 and 10-13.5-year-old groups (p &lt; 0.001). In the 6-9-yearold group, IR identified by a TG/HDL-C ratio ≥ 0.645 had a sensitivity, specificity, and an area under the curve (AUC) of 79.1%, 60.9%, and 0.734, respectively. In the 10–13.5-year-old group, IR identified by a TG/HDL-C ratio ≥ 0.725 had a sensitivity, specificity, and an AUC of 79.4%, 62.9%, and 0.724, respectively. Conclusion:: We showed the application of the TG/HDL-C ratio to predict insulin resistance in obese children in Beijing with different diagnostic thresholds based on age (6-9-year-old group with TG/HDL-C ≥ 0.645; 10–13.5-year-old group with TG/HDL-C ≥ 0.725), which were lower compared with the diagnostic threshold for insulin resistance in children reported in other countries.

ARE NEUTROPHIL/LYMPHOCYTE RATIO, LYMPHOCYTE/PLATELET RATIO, AND FERRITIN ASSOCIATED WITH INSULIN RESISTANCE IN OBESE WITH NORMAL ACUTE PHASE INDICATORS

Introduction: Obesity is a pro-inflammatory process that stimulates the release of inflammatory mediators. The aim of study is to investigate the relationship between insulin resistance and inflammation indicators of obesity, which are not often used in practice, in patients with excess weight. Methods: We conducted a cross-sectional study on 150 patients aged 18 years and older, whose acute phase values were within normal range and were admitted to the Internal Medicine Clinic due to excess weight. We divided the participants into four groups (G1, G2, G3, G4) based on obesity and insulin resistance (HOMA-IR), and analyzed inflammatory markers such as neutrophil lymphocyte ratio (NLR), lymphocyte platelet ratio (LPO) and ferritin. Results: The results showed that all chronic diseases were more common in the G4 group. In particular, there was a significant difference (p&lt;0.05) in the association between HT and hypothyroidism. Weight gain led to an increase in HOMA-IR (3.9±2.2), Ferritin levels (32; range 3-225), and NLO (1.8). Conclusion: This could serve as an inflammation indicator for the transition from obesity to chronic diseases.