Objective: Increased thyroid-stimulating hormone (TSH) and FT 3 levels are often found in clinically euthyroid obese individuals. Information on thyroid gene expression in human adipose tissue is scarce. The objective of this study was to measure the expression of the TSH receptor (TSHR) and the thyroid hormone receptor (TRa1) genes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese individuals and to test the effect of weight loss on these genes. Study Design and Participants: This study is a prospective study involving 107 obese (body mass index (BMI) ¼ 46±8 kg m À2 , 52 with type 2 diabetes or impaired glucose tolerance) and 12 lean nondiabetic participants. A total of 27 obese patients were restudied 1 year after gastric bypass surgery. Total RNA was extracted from SAT and VAT obtained at baseline from all participants, and from SAT in obese patients post surgery. Results: Circulating TSH and FT 3 levels were 170 and 36%, respectively, higher in obese patients than in controls. In SAT, TSHR and TRa1 were reduced in the obese by 67 and 33%, respectively, regardless of glucose tolerance. A similar trend was found in VAT. Post surgery, a BMI decrease of 33% was associated with a decrease in TSH and FT 3 levels and with a 150 and 70% increase in SAT of TSHR and TRa1, respectively. Conclusion: In both subcutaneous and visceral fat, the thyroid gene expression (especially TSHR) is reduced in obesity. The reversal of these changes with major weight loss and the reciprocal changes in plasma TSH and FT 3 levels suggest a role for adipocytes in the regulation of TSH and thyroid hormones.

Abstract3,5,3′-Levo-triiodothyronine (L-T3) is essential for DNA transcription, mitochondrial biogenesis and respiration, but its circulating levels rapidly decrease after myocardial infarction (MI). The main aim of our study was to test whether an early and sustained normalization of L-T3 serum levels after MI exerts myocardial protective effects through a mitochondrial preservation. Seventy-two hours after MI induced by anterior interventricular artery ligation, rats were infused with synthetic L-T3 (1.2 μg/kg/day) or saline over 4 weeks. Compared to saline, L-T3 infusion restored FT3 serum levels at euthyroid state (3.0 ± 0.2 versus 4.2 ± 0.3 pg/ml), improved left ventricular (LV) ejection fraction (39.5 ± 2.5 versus 65.5 ± 6.9%), preserved LV end-systolic wall thickening in the peri-infarct zone (6.34 ± 3.1 versus 33.7 ± 6.21%) and reduced LV infarct-scar size by approximately 50% (all P < 0.05). Moreover, L-T3 significantly increased angiogenesis and cell survival and enhanced the expression of nuclear-encoded transcription factors involved in these processes. Finally, L-T3 significantly increased the expression of factors involved in mitochondrial DNA transcription and biogenesis, such as hypoxic inducible factor-1α, mitochondrial transcription factor A and peroxisome proliferator activated receptor γ coactivator-1α, in the LV peri-infarct zone. To further explore mechanisms of L-T3 protective effects, we exposed isolated neonatal cardiomyocytes to H2O2 and found that L-T3 rescued mitochondrial biogenesis and function and protected against cell death via a mitoKATP dependent pathway. Early and sustained physiological restoration of circulating L-T3 levels after MI halves infarct scar size and prevents the progression towards heart failure. This beneficial effect is likely due to enhanced capillary formation and mitochondrial protection.

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Objective: To investigate whether adiponectin receptor genes (AdipoR1 and AdipoR2) expression in human subcutaneous (SAT) and visceral (VAT) adipose tissue in severely obese patients with or without diabetes is related to adiponectin gene (APM1) expression and in vivo metabolic parameters. Design: Cross-sectional, clinical research study. Subjects: Total RNA was extracted from SAT and VAT tissue obtained during surgery from 13 lean controls, 30 obese diabetic patients, 19 obese glucose-intolerant patients and 54 obese subjects with normal glucose tolerance. Measurements: Tissue expression of APM1, AdipoR1 and AdipoR2, tissue concentration of adiponectin (ApN), and metabolic variables. Results: APM1 expression was higher in SAT than VAT (1.0670.76 vs 0.6970.52, Po0.0001) as was AdipoR1 (1.1770.70 vs 0.6670.38, Po0.0001) and AdipoR2 (7.0276.19 vs 0.7570.64, Po0.0001). In SAT, APM1 and AdipoR1 expression tended to be lower -by 0.3870.22 and 0.3570.22, respectively -and AdipoR2 expression was markedly depressed -by 4.8271.93 -in association with obesity, whereas presence of diabetes had no additional effect. In VAT, APM1 and AdipoR1 expressions were also reduced -by 0.3670.16 and 0.3070.11, respectively -in association with obesity. Within both SAT and VAT, expression levels of APM1, AdipoR1 and AdipoR2 were all positively interrelated. Tissue ApN concentrations in SAT were similar across groups, whereas ApN levels in VAT were substantially lower in association with obesity (by an average of 63712 ng/mg total protein, Po0.0001). In multivariate models adjusting for sex, age and obesity, serum triglyceride concentrations were reciprocally related to APM1 (r ¼ À0.27, Po0.02), AdipoR1 (r ¼ À0.37, Po0.002 and AdipoR2 expression (r ¼ À0.37, Po0.002) in VAT. Likewise, plasma insulin concentrations were inversely related only to APM1 in VAT (r ¼ À0.25, Po0.03). Conclusions: Severe obesity is associated with suppressed expression of both ApN and its receptors in both SAT and VAT, the expression levels in VAT are specifically linked with hyperinsulinemia and dyslipidemia.