F-17 Dietary iron overload induces visceral adipose tissue insulin resistance and hyper-resistinemia, and synergizes with obesity and fatty liver in inducing systemic insulin resistance

Introduction: Myocardial infarction (MI) is the major cause of morbidity and mortality in the western world. Insulin resistance is a major complication in patients with MI. Hypothesis: Loss of visceral adipose tissue (VAT) resident macrophages in MI results in diminished adiponectin production causing systemic insulin resistance. Methods: To understand if MI results in insulin resistance, we analyzed UPMC patient records and identified patients who had normal fasting blood glucose levels on average 15 days before ST elevation myocardial infarction (STEMI) and checked their fasting blood glucose levels 30 days after STEMI. To understand the mechanisms of MI-induced insulin resistance, we used a mouse model of coronary ligation in C57BL/6 mice and analyzed the features of insulin resistance by measuring serum insulin, serum adiponectin, AKT activation status in the liver and muscle. Results: We found that 50% of non-diabetic patients (fasting blood glucose levels 99±2.5 mg/ dl) developed hyperglycemia (141±13 mg/dl) after MI, suggesting that MI causes insulin resistance. Consistently, mice with MI had higher fasting blood insulin, and reduced p-Akt levels in the liver and skeletal muscles confirming insulin resistance. Concomitantly, mice and patients with MI had reduced number of visceral adipose tissue (VAT) resident macrophages. In line with this, MI resulted in marked reduction in the level of macrophage colony stimulating factor (M-CSF), a cytokine required for tissue resident macrophage survival. M-CSF supplementation in mice with MI improved insulin sensitivity and decreased inflammatory phenotype of VAT macrophages. Furthermore, the systemic level of adiponectin, which is reported to augment insulin sensitivity, was profoundly reduced in mice after MI. Specific depletion of VAT resident macrophages resulted in lower levels of adiponectin in the serum, indicating that this macrophage subset is necessary for adiponectin production by adipocytes. Conclusions: Our data demonstrate that diminished M-CSF levels after MI triggers apoptosis of VAT resident macrophages, resulting in reduced adiponectin secretion and systemic insulin resistance.

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Relationship of visceral adipose tissue with surrogate insulin resistance and liver markers in individuals with metabolic syndrome chronic complications

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018820958298 ◽

2020 ◽

Vol 11 ◽

pp. 204201882095829

Author(s):

Vanessa Bullón-Vela ◽

Itziar Abete ◽

Josep A. Tur ◽

Jadwiga Konieczna ◽

Dora Romaguera ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Adipose Tissue ◽

Fatty Liver ◽

Visceral Adipose Tissue ◽

Chronic Complications ◽

Glutamyl Transferase ◽

Visceral Adipose ◽

Receiver Operating

Background: Visceral adipose tissue (VAT) has a hazardous influence on systemic inflammation, insulin resistance and an adverse metabolic profile, which increases the risk of developing non-alcoholic fatty liver disease (NAFLD) and chronic complications of diabetes. In our study we aimed to evaluate the association of VAT and the triglyceride glucose (TyG) as a proxy of insulin resistance surrogated with metabolic and liver risk factors among subjects diagnosed with metabolic syndrome (MetS). Methods: A cross-sectional study was performed including 326 participants with MetS (55–75 years) from the PREDIMED-Plus study. Liver-status markers, VAT and TyG were assessed. Participants were stratified by tertiles according to VAT ( n = 254) and TyG ( n = 326). A receiver operating characteristic curve was used to analyse the efficiency of TyG for VAT. Results: Subjects with greater visceral fat depots showed worse lipid profile, higher homeostatic model assessment for insulin resistance (HOMA-IR), TyG, alanine transaminase (ALT), fibroblast growth factor-21 (FGF-21), fatty liver index (FLI) and hepatic steatosis index (HSI) compared with participants in the first tertile. The multi-adjusted linear-regression analyses indicated that individuals in the third tertile of TyG (>9.1−10.7) had a positive association with HOMA-IR [ β = 3.07 (95% confidence interval (CI) 2.28−3.86; p trend < 0.001)], ALT [ β = 7.43 (95% CI 2.23−12.63; p trend = 0.005)], gamma glutamyl transferase (GGT) [ β = 14.12 (95% CI 3.64−24.61; p trend = 0.008)], FGF-21 [ β = 190.69 (95% CI 93.13−288.25; p trend < 0.001)], FLI [ β = 18.65 (95% CI 14.97−22.23; p trend < 0.001)] and HSI [ β = 3.46 (95% CI, 2.23−4.68; p trend < 0.001)] versus participants from the first tertile. Interestingly, the TyG showed the largest area under the receiver operating curve (AUC) for women (AUC = 0.713; 95% CI 0.62−0.79) compared with men (AUC = 0.570; 95% CI 0.48−0.66). Conclusions: A disrupted VAT enlargement and impairment of TyG are strongly associated with liver status and cardiometabolic risk factors linked with NAFLD in individuals diagnosed with MetS. Moreover, the TyG could be used as a suitable and reliable marker estimator of VAT.

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Association of Upper Trunk and Visceral Adipose Tissue Volume With Insulin Resistance in Control and HIV-Infected Subjects in the FRAM Study

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/qai.0b013e31814b94e2 ◽

2007 ◽

Vol 46 (3) ◽

pp. 283-290 ◽

Cited By ~ 73

Author(s):

Carl Grunfeld ◽

David Rimland ◽

Cynthia L Gibert ◽

William G Powderly ◽

Stephen Sidney ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Tissue Volume ◽

Adipose Tissue Volume ◽

Visceral Adipose

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Overexpression of 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non-alcoholic fatty liver disease

Liver International ◽

10.1111/j.1478-3231.2011.02685.x ◽

2011 ◽

pp. n/a-n/a ◽

Cited By ~ 3

Author(s):

Roberto Candia ◽

Arnoldo Riquelme ◽

Rene Baudrand ◽

Cristian A. Carvajal ◽

Mauricio Morales ◽

...

Keyword(s):

Adipose Tissue ◽

Liver Disease ◽

Fatty Liver ◽

Visceral Adipose Tissue ◽

Fatty Liver Disease ◽

Hydroxysteroid Dehydrogenase ◽

Alcoholic Fatty Liver ◽

Visceral Adipose ◽

Alcoholic Fatty Liver Disease

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Elevated serum uric acid is a facilitating mechanism for insulin resistance mediated accumulation of visceral adipose tissue

10.1101/2020.09.20.20198499 ◽

2020 ◽

Author(s):

Luisa Fernández-Chirino ◽

Neftali Eduardo Antonio-Villa ◽

Arsenio Vargas-Vázquez ◽

Paloma Almeda-Valdés ◽

Donají Gómez-Velasco ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Uric Acid ◽

Serum Uric Acid ◽

Visceral Adipose Tissue ◽

Visceral Obesity ◽

Causal Mechanism ◽

Mediation Analyses ◽

Bidirectional Relationship ◽

Visceral Adipose

BACKGROUND: Serum uric acid (SUA) has a relationship with cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation. Here, we aimed to clarify the nature of this relationship and the underlying causality mechanism. METHODS: We conducted a population-based cross-sectional study comprising 8,504 subjects joining both NHANES 2003-2004 and 2011-2012 cycles and ENSANUT Medio Camino 2016. We performed mixed effects linear regression models using HOMA2-IR, adipoIR, and METS-VF as indicators of IR and VAT accumulation. Furthermore, we performed mediation analyses to assess a potential causal mechanism and ROC curves to establish cut-off points for identification of IR and visceral obesity using SUA. Finally, with an additional dataset comprised of 226 subjects with both euglycemic hyperinsulinemic clamp (EHC) and dual X-ray absorptiometry (DXA) measurements for IR and VAT accumulation, we performed a network of confirmatory mediation analyses. RESULTS:We found that SUA has a mediating role inside the bidirectional relationship between IR and visceral obesity, and it is part of an underlying causality mechanism which includes adiponectin. The proportion of the mechanism mediated by SUA is greater when stated that IR (in either peripheral or adipose tissue) leads to VAT accumulation (14.90%[13.20%-17.00%] and 15.54%[13.61% - 18.00%] to 4.88%[3.06%-7.00%] and 8.13%[5.91% - 10.00%]) instead of the opposite direction. This result was confirmed by mediation analyses using gold-standard measurements. CONCLUSIONS:Elevated SUA acts as mediator inside the bidirectional relationship between IR andVAT accumulation. Its role appears to be larger when considering adipose tissue IR as the promoter for VAT accumulation.

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Protocatechuic acids protects against high glucose- induced insulin resistance in human visceral adipose tissue

Problems of Endocrinology ◽

10.14341/probl201662545-46 ◽

2016 ◽

Vol 62 (5) ◽

pp. 45-46

Author(s):

Paulina Ormazabal ◽

Beatrice Scazzocchio ◽

Rosaria Varì ◽

Annunziata Iacovelli ◽

Roberta Masella

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

High Glucose ◽

Protective Role ◽

Insulin Sensitizer ◽

20 Nm ◽

Visceral Adipose

Adipocytes exposed to high glucose concentrations exhibit impaired insulin signaling. Binding of insulin to its membrane receptor activates insulin metabolic pathway leading to IRS-1 and AKT phosphorylations. The accumulation of visceral adipose tissue (VAT) correlates with insulin resistance and metabolic syndrome. Anthocyanins (ACN) are bioactive food compounds of great nutritional interest. We have shown that protocatechuic acid (PCA), a major metabolite of ACN, might exert insulin-sensitizer activities in human visceral adipose tissue. The aim of this work was to define the protective role of PCA against insulin-resistance induced by high glucose in VAT.Methodology: VAT obtained from control subject (BMI≤25) were separated in four experimental groups: i) PCA: samples treated for 24 h with 100 μM PCA, ii) GLU: VAT treated with 30 mM glucose for 24 h, iii) PCA+GLU: 1 hour incubation with 100 μM PCA before adding glucose (30 mM, 24 h), iv) CTR: vehicle. After treatment, VAT groups were (or not) acutely stimulated with insulin (20 nM, 20 min). Tyr-IRS-1 and Ser-Akt phosphorylations were assessed by Western blotting (WB) in basal or insulin stimulated tissues in all experimental groups. Samples were assessed for IRS-1, IR, Akt and GLUT4 protein content by WB. Results: No differences in protein contents between experimental groups were found. GLU tissues showed a lower increment in insulin-stimulated phosphorylation of IRS-1 and Akt compared to CTR and PCA samples. This impaired activation was completely reversed by the pretreatment with PCA.Conclusion: An in-vitro insulin-resistance condition induced by high glucose was established in biopsies of VAT. PCA restores the ability of GLU-tissues to fully respond to insulin by increasing IRS-1 and Akt phosphorylations. These results confirm the insulin-sensitizer effect of PCA on VAT previously reported by our group. An anthocyanin rich diet might help to protect against insulin-resistance in VAT.

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