Bariatric Surgery Is Accompanied by Changes in Extracellular Vesicle-Associated and Plasma Fatty Acid Binding Protein 4.

BACKGROUND: Bariatric surgery markedly reduces fat mass with beneficial effects on cardiometabolic health but the mechanisms involved are not fully understood. Extracellular vesicles (EVs) are secreted by a variety of cells, including adipocytes, and may mediate some of these benefits. However, the effects of bariatric surgery on circulating EVs are unclear. METHODS: Concentration of plasma EVs isolated by ultracentrifugation at baseline, 1 and 6 months post-bariatric surgery (n = 20) was established using Nanoparticle Tracking Analysis. EV origin (CD9: exosome; CD41: platelet; CD235a: erythrocyte; CD11b: leukocyte; CD144: endothelial), cytokine (interferon γ, interleukin-6, TNF-α) and adipocyte marker (adiponectin, FABP4, PPARγ) expression was measured by time-resolved fluorescence immunoassay. RESULTS: EV concentration and cell-of-origin markers (CD41, CD235a, CD11b, CD144) did not alter in response to surgery, neither did EV-expressed interferon γ, IL-6, TNF-α, adiponectin, PPARγ or CD9. EV-derived fatty acid binding protein 4 (FABP4) increased at 1 month (+ 49%) before returning to baseline by 6 months (- 51%, p < 0.05), corresponding to similar changes in circulating plasma FABP4 (+ 22 and - 24% at 1 and 6 months, respectively; p < 0.001). Patients who underwent biliopancreatic diversion had lower FABP4-expressing EVs at 6 months compared to those who underwent sleeve gastrectomy/gastric banding (p < 0.05), despite similar percentage weight reduction (- 19 vs - 20%, respectively). CD9 expression correlated with EV-expressed FABP4, adiponectin, TNF-α and interferon γ (r = 0.5, r = 0.59, r = 0.53, r = 0.41, respectively, p < 0.005), suggesting transport by an EV population of exosomal rather than microvesicular origin. CONCLUSIONS: Bariatric surgery leads to a transient change in circulating EV- and plasma-derived FABP4, reflecting alterations in adipose tissue homeostasis.

Preconception thyroid-stimulating hormone and pregnancy outcomes in women with hypothyroidism.

OBJECTIVES: Maternal hypothyroidism may adversely affect pregnancy outcomes. International practice guidelines recommend that women with hypothyroidism should attain a preconception and early gestation serum thyroid-stimulating hormone (TSH) level of <2.5 mU/L. Our objective was to ascertain what proportion of women realize this target in practice and whether a TSH level above this threshold has adverse fetal and maternal consequences. METHODS: This was an observational study of women with hypothyroidism referred to an endocrine antenatal clinic between 2008 and 2010 (n = 78; mean age, 30.4 years; range, 19 to 43 years). Thyroid profiles (free thyroxine [FT4] and TSH) before conception and through pregnancy were documented. Obstetrics outcomes were examined, including low birth weight, preterm births, preeclampsia, caesarean sections, and admissions to special care neonatal units. RESULTS: Thyroid testing was undertaken in 80% of subjects before conception, and in 64, 94, and 96% of subjects in the first, second, and third trimesters of pregnancy, respectively. TSH >2.5 mU/L was seen in 49% of women before conception and in 68% of women in the first trimester. Six women were overtly hypothyroid before conception, attaining normal thyroid function at gestational ages ranging from 12 to 36 weeks. Neither the preconception nor the first postconception TSH level (>2.5 mU/L or ≤2.5 mU/L) was associated with gestational age at delivery, birth weight, or rates of caesarean section or preeclampsia. CONCLUSION: The majority of women with hypothyroidism do not achieve the recommended preconception and early gestation TSH targets. Preconception and early gestation TSH >2.5 mU/L was not associated with adverse fetal and maternal outcomes. Studies in larger cohorts will be required to confirm these findings, however.