Insulin Sensitivity Biomarkers Research Articles

Effects of resistance exercise and whey protein supplementation on cognitive function in older men: secondary analysis of a randomised, double-blind, placebo-controlled trial

PurposeAgeing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation (PRO) on cognitive function in older men. MethodsIn a pooled-groups analysis, 36 older men (age: 67 ± 4 years) were randomised to either RE (2 x/week; n = 18) or no exercise (NE; n = 18), and either PRO (2 × 25 g/d whey protein isolate; n = 18) or control (CON, 2 × 23.75 g maltodextrin/d; n = 18). A sub-analysis was also conducted between RE + CON (n = 9) and RE + PRO (n = 9). At baseline and 12 weeks, participants completed a battery of neuropsychological tests (CANTAB; Cambridge Cognition, UK) and neurobiological, inflammatory, salivary cortisol and insulin sensitivity biomarkers were quantified. ResultsPRO improved executive function z-score (+0.31 ± 0.08) greater than CON (+0.06 ± 0.08, P = 0.03) and there was a trend towards improved global cognitive function (P = 0.053). RE and RE + PRO did not improve any cognitive function domains (p ≥ 0.07). RE decreased tumor necrosis factor-alpha (P = 0.02) and interleukin-6 (P = 0.048) concentrations compared to NE, but changes in biomarkers did not correlate with changes in cognitive domains. Muscle strength (r = 0.34, P = 0.045) and physical function (ρ = 0.35–0.51, P < 0.05) outcomes positively correlated with cognitive function domains at baseline, but only Δskeletal muscle index correlated with Δepisodic memory (r = 0.34, P = 0.046) following the intervention. ConclusionIn older men, PRO improved cognitive function, most notably executive functioning. RE did not improve any cognitive function domains but did decrease biomarkers of systemic inflammation. No synergistic effects were observed.

Adiponectin, IGFBP-1 and -2 are independent predictors in forecasting prediabetes and type 2 diabetes.

Adiponectin and insulin-like growth factor (IGF) binding proteins IGFBP-1 and IGFBP-2 are biomarkers of insulin sensitivity. IGFBP-1 reflects insulin sensitivity in the liver, adiponectin in adipose tissue and IGFBP-2 in both tissues. Here, we study the power of the biomarkers adiponectin, IGFBP-1, IGFBP-2, and also included IGF-I and IGF-II, in predicting prediabetes and type 2 diabetes (T2D) in men and women with normal oral glucose tolerance (NGT). Subjects with NGT (35-56 years) recruited during 1992-1998 were re-investigated 8-10 years later. In a nested case control study, subjects progressing to prediabetes (133 women, 164 men) or to T2D (55 women, 98 men) were compared with age and sex matched NGT controls (200 women and 277 men). The evaluation included questionnaires, health status, anthropometry, biochemistry and oral glucose tolerance test. After adjustment, the lowest quartile of adiponectin, IGFBP-1 and IGFBP-2 associated independently with future abnormal glucose tolerance (AGT) in both genders in multivariate analyses. High IGFs predicted weakly AGT in women. In women, low IGFBP-2 was the strongest predictor for prediabetes (OR:7.5), and low adiponectin for T2D (OR:29.4). In men, low IGFBP-1 was the strongest predictor for both prediabetes (OR:13.4) and T2D (OR:14.9). When adiponectin, IGFBP-1 and IGFBP-2 were combined, the ROC-AUC reached 0.87 for women and 0.79 for men, higher than for BMI alone. Differences were observed comparing adipocyte- and hepatocyte-derived biomarkers in forecasting AGT in NGT subjects. In women the strongest predictor for T2D was adiponectin and in men IGFBP-1, and for prediabetes IGFBP-2 in women and IGFBP-1 in men.

715-P: Tirzepatide as Monotherapy Improved Markers of Beta-Cell Function and Insulin Sensitivity in People with Type 2 Diabetes (SURPASS-1)

Tirzepatide (TZP) , a novel dual GIP/GLP-1 receptor agonist, led to greater HbA1c, fasting serum glucose and body weight reductions vs. placebo (PBO) in people with early T2D (baseline mean T2D duration 4.7 y and 54% no prior diabetes medications) from the 40-wk SURPASS-1 trial. In a Phase 2b trial, TZP also improved β-cell function and insulin sensitivity (IS) vs. PBO and selective GLP-1 receptor agonist, dulaglutide 1.5 mg. Similarly, in SURPASS-1, TZP improved β-cell function, as indicated by a 75-80% increase in HOMA2-B, and insulin resistance, as indicated by a 2-12% decrease in fasting insulin and 8-20% decrease in HOMA2-IR. In this analysis, we aimed to explore changes in additional biomarkers of β-cell function and IS after TZP monotherapy (5, and 15 mg) . At 40 wks, proinsulin/C-peptide ratios, a marker of insulin processing, β-cell stress and β-cell function improved with decrease by 47-49% with TZP vs. -0.1% with PBO (p&amp;lt;0.001, all doses) (Table) . Fasting proinsulin decreased by 49-55% with TZP vs. no change with PBO (p&amp;lt;0.001, all doses) . Decreases in fasting C-peptide by 3-9% with TZP did not differ vs. PBO. TZP vs. PBO improved biomarkers of IS evidenced by increases in adiponectin (16-23% vs. -0.2%; p≤0.028, all doses) and IGFBP-2 (38-70% vs. 4.1%; p&amp;lt;0.001, all doses) . As a monotherapy for early T2D, TZP achieved significant improvement in markers of β-cell function and IS. Disclosure C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. H.Mao: Employee; Eli Lilly and Company. V.Thieu: None. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

Predictors of normalized HbA1c after gastric bypass surgery in subjects with abnormal glucose levels, a 2-year follow-up study

Clinical biomarkers can predict normalization of HbA1c after Roux-en-Y gastric bypass (RYGB) surgery, but it is unclear which are the most predictive.The aim of this study was to compare biomarkers for insulin sensitivity and other clinical parameters in the prediction of normalization of HbA1c after RYGB surgery. This study included 99 (23 men) obese subjects (BMI > 35 kg/m2) undergoing a laparoscopic RYGB. Clinical and biochemical examinations were performed pre-operatively and up to 2 years after surgery. Pre-operatively, normal fasting glucose levels were found in 25 individuals (NG), prediabetes in 46 and type 2 diabetes (T2DM) in 28. At baseline IGF-I (SD), IGFBP-1 and adiponectin levels were low while leptin was high. Weight loss was observed in all three groups, most in the prediabetes group. After 2 years HbA1c was decreased in prediabetes and T2DM. In all three groups insulin, HOMA-IR, lipids and blood pressure improved, IGFBP-1 and adiponectin increased and leptin decreased. IGF-I (SD) increased only in T2DM. In those with prediabetes or T2DM (n = 74), HbA1c at 2 years correlated to baseline BMI (r = -0.27, p = 0.028), age (r = 0.43, p < 0.001), HbA1c (r = 0.37, p = 0.001) and IGFBP-1 (r = 0.25, p = 0.038), and was normalized in 45/74 (61%) at 1 year and in 36 subjects (49%) at 2 years. These responders were younger, had higher BMI, larger waist circumference, lower HbA1c and lower IGFBP-1 levels at baseline. In a multiple regression model age (negative, p = 0.021) and waist circumference (positive, p = 0.047) were the only predictors for normalized HbA1c. RYGB normalized HbA1c in 49% at two years follow-up, which was predicted by low baseline IGFBP-1 level, a marker of hepatic insulin sensitivty and insulin secretion. However,. younger age and larger waist circumference were the only predictors of normalized HbA1c in multivariate analysis.

MTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis

mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation. Evidence in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate response element binding protein (ChREBP) activity, histone acetylation, and gluco-lipogenic gene expression. Substrate utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate through acetyl-CoA synthetase 2 (ACSS2). These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-CoA synthesis.

2048-P: The Physiological Effects of VLCD in Overweight Nondiabetics

Background: Very Low-Calorie Diets (VLCD) are being increasingly used as a treatment for obesity and diabetes, yet concerns persist regarding reductions in muscle mass (as a crucial locomotory and insulin sensitive organ), while many physiological effects of VLCD are ill-defined. We thus explored the effects of VLCD on body composition, insulin sensitivity and vascular function in the overweight. Methods: Eight overweight men (47±7y; 103±14kg; BMI 32±4, mean±SD) were placed on a VLCD, of &amp;lt;800kcal/day for 6-weeks via meal replacements. Before/after VLCD, we conducted: OGTT, DXA to quantity fat and lean body mass, ultrasound (U.S.) to determine flow-mediated dilatation (FMD), and echocardiogram (ECHO) for left ventricular function (LVF). Insulin sensitivity was assessed via: i) HOMA-IR ii) area under the curve (AUC) for insulin and glucose iii) QUICKI iv) Matsuda Index. Results: VLCD reduced body weight (∆ -10.5±3 kg), fat mass (∆ -6.8±2 kg) and lean body mass (∆ -4.1±2 kg); all p&amp;lt;0.001. Significant improvements occurred in insulin sensitivity (HOMA-IR ∆ -0.6 ±0.6; AUC insulin ∆ -2147±2153 miliU/L*minute; QUICKI ∆ +0.05±0.03, and Matsuda Index ∆ 5.4±3.5); all P&amp;lt;0.05). No significant differences were observed in FMD (∆ 0.5±1.7%, P=0.5), LVF (∆ 1.4 ±6.9%, P=0.6), or AUC glucose (∆ -23.3±167.2 mmol/L*minute, P=0.7). No correlation was evident between degree of insulin sensitivity biomarkers and body weight or fat loss (e.g., Pearson -0.1&amp;lt;r&amp;lt;0.1, P&amp;gt;0.8). Conclusion: VLCD predictably induced marked weight loss and improved insulin sensitivity during just 6-weeks of VLCD, and this was associated with body fat loss and muscle wasting. Nonetheless, the poor correlation between total weight or body fat loss and improved indices of insulin action points to metabolic reprogramming of insulin sensitive tissues in response to energy restriction, rather than fat loss per se, in driving some of the health benefits of VLCD. Developing means to mitigate muscle atrophy with VLCD is crucial to maximizing therapeutic benefits, especially in aging. Disclosure M. Abdul Aziz: None. B.E. Phillips: None. I. Ramzan: None. J. Cegielski: None. K. Smith: None. I.R. Idris: None. P.J. Atherton: None. Funding Medical Research Council UK

Plasma lactate and leukocyte mitochondrial DNA copy number as biomarkers of insulin sensitivity in non-diabetic women.

High plasma lactate levels have been associated with reduced mitochondrial respiratory capacity and increased type 2 diabetes risk, while mitochondrial DNA (mtDNA) copy number has been proposed as a biomarker of mitochondrial function linked to glucose homeostasis. The aim of this study was to evaluate the association between circulating lactate levels and leukocyte mtDNA copy numbers with insulin secretion/sensitivity indexes in 65 Chilean non-diabetic women. mtDNA copy numbers were measured in leukocytes using qPCR and digital-droplet PCR. A 75-g Oral Glucose Tolerance Test (OGTT) was performed to calculate systemic and tissue-specific insulin sensitivity indexes, as well as insulin secretion surrogates based on plasma c-peptide. An intravenous glucose tolerance test (IVGTT; 0.3g/kg) was also carried out. Disposition indexes were calculated as the product of insulin secretion × sensitivity. Plasma levels of leptin, adiponectin, TNF-α, MCP-1, and non-esterified fatty acids were also determined. Fasting plasma lactate shows a significant association with a wide range of insulin sensitivity/resistance indexes based on fasting plasma samples (HOMA-S, adipose IR index, Revised-QUICKI, leptin-adiponectin ratio, TyG index, McAuley index and TG-to-HDL-C ratio), as well as OGTT-based measures such as the Matsuda index, the hepatic insulin resistance index, and the disposition index. Fasting plasma lactate was also positively associated with the circulating adipokines TNF-α and MCP-1. We also detected a direct association between fasting plasma lactate with leukocyte mtDNA copy numbers. The above results support the use of fasting plasma lactate, and possibly leukocyte mtDNA copy numbers, as biomarkers of reduced oxidative mitochondrial capacity, decreased hepatic insulin sensitivity, and future diabetes risk.

Adiponectin concentration data improve the estimation of atherosclerotic risk in normal and in overweight subjects.

The combinations of adipokines and body mass parameters to estimate carotid atherosclerotic disease have not been completely delineated. To test the combinations of well-established, easily accessible body mass indices and circulating biomarkers to identify increased carotid intima-media thickness (cIMT) in a primary prevention setting. In a cross-sectional analysis of 339 asymptomatic individuals with no history of cardiovascular events, inflammatory and insulin sensitivity biomarkers as well as adipokine levels were measured and combined with body mass parameters to evaluate the best marker for increased cIMT. As isolated parameters, body mass index (BMI) and adiponectin best identified abnormal cIMT (P=.04). Adiponectin levels were also linked to the relationship between BMI and cIMT (β=0.0371; P=.01). Twenty-nine individuals with increased cIMT were missed by BMI alone but detected by combining BMI and adiponectin measurements. When compared with BMI alone, the combination of adiponectin plus BMI improved the c-statistic (0.549-0.567) and the integrated discrimination improvement index (0.01725; P=.021). Segregation of individuals by the combined use of BMI+adiponectin is associated with significant differences in insulin sensitivity, glomerular filtration rate, systemic inflammatory activity, dyslipidaemia and cIMT. Combining plasma adiponectin measurements and BMI improves estimation of cIMT as compared to anthropometric parameters.

Effect of vitamin D on stress-induced hyperglycaemia and insulin resistance in critically ill patients.

Effects of vitamin D supplementation on the glycaemic indices and insulin resistance in diabetic and non-diabetic patients were studied. In this study, effects of vitamin D supplementation on stress-induced hyperglycaemia and insulin resistance were evaluated in non-diabetic surgical critically ill patients. Adult surgical patients with stress-induced hyperglycaemia within the first 24 h of admission to the ICU were recruited. The patients randomly assigned to receive either vitamin D or placebo. Patients in the vitamin D group received a single dose of 600,000 IU vitamin D3 as intramuscular injection at time of recruitment. Besides demographic and clinical characteristics of the patients, plasma glucose, insulin, 25(OH) D and adiponectin levels were measured at the time of ICU admission and day 7. Homoeostasis model assessment for insulin resistance (HOMA-IR) and homestasis model assessment adiponectin (HOMA-AD) ratio were considered at the times of assessment. Comparing with the baseline, plasma 25(OH) D level significantly increased in the subjects who received vitamin D (p = 0.04). Improvement in fasting plasma glucose levels was detected in day 7 of the study compared with the baseline status in both groups. HOMA-IR showed a decrement pattern in vitamin D group (p = 0.09). Fasting plasma adiponectin levels increased significantly in the vitamin D group (p = 0.007), but not in the placebo group (p = 0.38). Finally, changes in HOMA-AD ratio were not significant in the both groups. Vitamin D supplementation showed positive effect on plasma adiponectin level, as a biomarker of insulin sensitivity in surgical critically ill patients with stress-induced hyperglycaemia. However, effects of vitamin D supplementation on HOMA-IR and HOMA-AD as indicators of insulin resistance were not significant.

Pharmacologic androgen deprivation and cardiovascular disease risk factors: a systematic review.

Pharmacologic androgen deprivation therapy (ADT) is widely used to treat prostate cancer. Observational studies suggest ADT is associated with cardiovascular disease and its risk factors; however, such studies may be subject to bias. Our objective was to evaluate the effect of ADT on cardiovascular disease risk factors using data from randomized controlled trials (RCTs). We conducted a systematic review using MEDLINE and MEDLINE In-Process (1950-June 2013), EMBASE (1974-June 2013) and Web of Science (1900-June 2013) for all RCTs in men with prostate cancer that compared pharmacologic ADT (i.e. use of gonadotropin-releasing hormone agonist or antagonist) with a group that did not receive ADT and reported data on cardiovascular disease risk factors including blood pressure, cholesterol, triglycerides, fibrinogen, biomarkers of insulin sensitivity, adiposity and C-reactive protein. We also searched for ongoing or unpublished trials. This study was registered at the PROSPERO International Prospective Register of Systematic Reviews (CRD42013005035). Of the 3272 unique publications identified in our systematic review, we did not identify a single RCT that reported data on any cardiovascular disease risk factor. We were unable to locate unreported data from corresponding authors or study sponsors. There is a lack of published, reliable evidence describing the effects of ADT on cardiovascular disease risk factors. RCTs have likely collected data on these risk factors as part of routine study monitoring; however, these data have not been published. To understand the effect of ADT on cardiovascular morbidity, these data must be made available to the scientific community.

Soluble CD163 Is Associated With CD163 mRNA Expression in Adipose Tissue and With Insulin Sensitivity in Steady-State Condition but Not in Response to Calorie Restriction

Soluble CD163 (sCD163) was suggested as a biomarker of insulin sensitivity and CD163 mRNA expression representing macrophage content in adipose tissue (AT). The aim of this study was to investigate, in cross-sectional and prospective design, the relationship between sCD163 circulating levels and CD163 mRNA expression in adipose tissue and insulin sensitivity assessed by euglycemic-hyperinsulinemic clamp. Two cohorts of subjects were examined in the study. Cohort 1 included 42 women with a wide range of body mass index (17-48 kg/m(2)); cohort 2 included 27 obese women who followed a dietary intervention consisting of 1 month of a very low-calorie diet and 5 months of a weight-stabilization period. Serum levels of CD163 and mRNA expression of CD163 and CD68 in sc and visceral (visc) AT were determined, and insulin sensitivity [expressed as glucose disposal rate (GDR)] was measured in cohort 1. In cohort 2, serum levels of CD163, mRNA expressions of CD163, CD68, and CD163-shedding factors [TNF-α-converting enzyme (TACE) and tissue inhibitor of metalloproteinase (TIMP3)] in sc AT were examined and GDR was measured before and during dietary intervention. In cohort 1, circulating sCD163 correlated with CD163 mRNA levels in both sc and visc AT. sCD163 and CD163 mRNA expression in both fat depots correlated with GDR. In cohort 2, the diet-induced changes of sCD163 levels did not correlate with those of CD163, CD68, TACE, and TIMP3 mRNA levels. Although the pattern of the diet-induced change of sCD163 paralleled that of GDR, there was no correlation between the changes of these two variables. sCD163 correlates with CD163 mRNA expression in sc and visc AT and with whole-body insulin sensitivity in the steady-state condition. These associations are not observed with respect to the diet-induced changes during a weight-reducing hypocaloric diet.

Abstract A61: Smoking modifies the association of insulin sensitivity biomarkers and pancreatic cancer risk

Abstract Cigarette smoking is the most important known risk factor for pancreatic cancer. Smoking leads to imbalances in metabolic hormones that are conducive to insulin resistance. Cigarette smoke also damages the exocrine pancreas, which can lead to pancreatogenic diabetes, also known as Type 3c diabetes mellitus (T3cDM). In contrast to type 2 diabetes mellitus (T2DM), which is associated with obesity and characterized by high levels of C-peptide, a marker of insulin secretion, T3cDM is characterized by low C-peptide concentrations, reflecting low pancreatic function. High Molecular Weight (HMW) adiponectin, on the other hand, is the most biologically active isoform of the insulin-sensitizing hormone adiponectin, and is inversely associated with obesity and T2DM incidence. We evaluated the association of serum biomarkers [C-peptide, adiponectin, and HMW adiopnectin] and pancreatic cancer by smoking status in a nested case control study of 759 cases and 1069 controls from the Alpha-Tacopherol, Beta Carotene Cancer Prevention Study (ATBC n=888), the Cancer Prevention Study II Nutrition Cohort (CPS II n=180), and the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO n=760). Controls were matched to cases on age, date of blood draw (+ 3 months), sex, and race and were free from pancreatic cancer on the date the matched case was diagnosed. Spline regression models were used to examine the possible non-linear relation between the biomarkers and pancreatic cancer risk and logistic regression stratified on smoking status was used to calculate odds ratios and 95% confidence intervals. Smoking status modified the association of pancreatic cancer risk and prediagnostic C-peptide (p interaction=0.009) and HMW adiponectin (p interaction=0.02). Prediagnostic C-peptide concentration was inversely associated with pancreatic cancer in smokers [Odds Ratio = 0.76 (95% Confidence Interval = 0.63-, 0.91) per standard deviation], while no association was found in non-smokers [1.09 (0.96, 1.24)]. Similarly, prediagnostic HMW adiponectin concentration was associated with increased risk in smokers [1.23 (1.02, 1.47)]. As expected, HMW adiponectin tended to be inversely associated with pancreatic cancer risk in non-smokers [0.81 (0.63, 1.05)]. Spline analysis showed that both the association of C-peptide (p=0.01) and HMW (p=0.004) with pancreatic cancer risk were linear. Total adiponectin was not associated with pancreatic cancer risk either in smokers or non-smokers. Our findings with c-peptide and HMW adiponectin may be consistent with Type 3c diabetes which has recently been recognized to play a role in pancreatic carcinogenesis. In smokers, low C-peptide concentration may reflect low pancreatic function from smoke-induced damage to the pancreas, which is concordant with increased pancreatic cancer risk. Given the functional interaction between hormone-secreting pancreatic cells and adipocytes, HMW adiponectin concentration is a marker for peripheral insulin sensitivity and may be elevated to compensate for diminished pancreatic function. Hence, the positive association for both low C-peptide and high HMW adiponectin with pancreatic cancer in smokers supports the notion that cigarette smoking both decreases pancreatic function leading to pancreatogenic diabetes and increases pancreatic cancer risk. These results suggest that the associations of C-Peptide and HMW Adiponectin with pancreatic cancer may be more complex than previously appreciated and differ according to smoking status. A better understanding of the metabolic profile of smokers may be helpful in identifying high-risk individuals who could be targeted for pancreatic cancer prevention interventions. Citation Format: Leticia Nogueira, Christina Newton, Debra Silverman, Demetrius Albanes, Satu Manniston, Eric Jacobs, Rachel Stolzemberg-Solomon. Smoking modifies the association of insulin sensitivity biomarkers and pancreatic cancer risk. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A61.

Inflammation and insulin resistance exert dual effects on adipose tissue tumor protein 53 expression

The purpose of this study was to investigate the expression of human adipose tissue protein 53 (p53) in subjects who varied widely in terms of obesity and insulin resistance. We also analyzed different in vivo and in vitro models to try to comprehend the associations found in humans. p53 was analyzed in human adipose and isolated adipocytes, in high fat-fed and GLP-1R KO mice, during in vitro adipogenesis, and in adipocytes after high glucose, rosiglitazone and inflammatory conditions. The effects of surgery-induced weight loss and ex vivo metformin were also evaluated. Omental (OM) p53 gene expression (+27%, P=0.001) and protein (+11%, P=0.04) were increased in obese subjects and high fat diet-induced obese mice (+86%, P=0.018). Although the obesity-associated inflammatory milieu was associated with increased OM p53, this was negatively related to insulin resistance and glycated hemoglobin, and positively with biomarkers for insulin sensitivity. Multiple linear regression analyses revealed that glycated hemoglobin (P<0.0001) and body mass index (P=0.048) contributed independently to explain 13.7% (P<0.0001) of the OM p53 variance. Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53. While the glucose-intolerant GLP-1R KO mice showed decreased mesenteric p53 (-45.4%, P=0.017), high glucose led to decreased p53 in pre-adipocytes (-27%, P<0.0001). Inflammatory treatments led to increased p53 (+35%, P<0.0001), while Rs downregulated this expression (-40%, P=0.005) in mature adipocytes. Inflammation and insulin resistance exert dual effects on adipose p53, which seems to be the final result of these opposing forces.

Impacto hormonal e inflamatório de diferentes composições dietéticas: ênfase em padrões alimentares e fatores dietéticos específicos

Healthy dietary pattern, characterized by the consumption of fruits, vegetables, white meats, skim dairy products, nuts and moderate intake of vegetable oils and alcohol, is an important factor for a lower risk of chronic disease such as obesity, metabolic syndrome and cardiovascular disease. This beneficial effect can be explained, at least partially, by its modulating role on biomarkers of insulin sensitivity and atherosclerosis as well as of inflammation and endothelial function. On the other hand, the intake of specific dietary factors, such as unsaturated fatty acids (oleic and alpha-linolenic) and micronutrients with antioxidant properties (vitamins A, E and C; selenium, zinc) has been discussed, due to its potential protector action due to chronic disease occurrence and its possible profits in hormonal, metabolic and inflammatory regulations that these dietetic factors can provide within a nutritional treatment to obesity and metabolic syndrome.