MiR-19 Family Impairs Adipogenesis by the Downregulation of the PPARγ Transcriptional Network.

microRNAs (miRNAs) are a class of small endogenous RNA that play pivotal roles in both the differentiation and function of adipocytes during the development of obesity. Despite this, only a few miRNA families have been identified as key players in adipogenesis. Here, we show the relevance of the miR-19 family, miR-19a and miR-19b, in lipid accumulation and the expansion of the adipose tissue in obesity. We observed that miR-19s were upregulated in the abdominal subcutaneous adipose tissue (aSAT) of human patients with morbid obesity, whereas after bariatric surgery, their expression was reduced. In vitro experiments identified miR-19a and b as crucial actors in adipogenesis and lipid accumulation. Overall, our results suggest a novel role of the miR-19 family in the regulatory networks underlying adipogenesis and, therefore, adipose tissue dysfunction.

Metabolic recovery after weight loss surgery is reflected in serum microRNAs.

INTRODUCTION: Bariatric surgery offers the most effective treatment for obesity, ameliorating or even reverting associated metabolic disorders, such as type 2 diabetes. We sought to determine the effects of bariatric surgery on circulating microRNAs (miRNAs) that have been implicated in the metabolic cross talk between the liver and adipose tissue. RESEARCH DESIGN AND METHODS: We measured 30 miRNAs in 155 morbidly obese patients and 47 controls and defined associations between miRNAs and metabolic parameters. Patients were followed up for 12 months after bariatric surgery. Key findings were replicated in a separate cohort of bariatric surgery patients with up to 18 months of follow-up. RESULTS: Higher circulating levels of liver-related miRNAs, such as miR-122, miR-885-5 p or miR-192 were observed in morbidly obese patients. The levels of these miRNAs were positively correlated with body mass index, percentage fat mass, blood glucose levels and liver transaminases. Elevated levels of circulating liver-derived miRNAs were reversed to levels of non-obese controls within 3 months after bariatric surgery. In contrast, putative adipose tissue-derived miRNAs remained unchanged (miR-99b) or increased (miR-221, miR-222) after bariatric surgery, suggesting a minor contribution of white adipose tissue to circulating miRNA levels. Circulating levels of liver-derived miRNAs normalized along with the endocrine and metabolic recovery of bariatric surgery, independent of the fat percentage reduction. CONCLUSIONS: Since liver miRNAs play a crucial role in the regulation of hepatic biochemical processes, future studies are warranted to assess whether they may serve as determinants or mediators of metabolic risk in morbidly obese patients.

Central Resistance to Thyroid Hormones in Morbidly Obese Subjects Is Reversed after Bariatric Surgery-Induced Weight Loss.

Endocrine abnormalities are common in obesity, including altered thyroid function. The altered thyroid function of obesity may be due to a mild acquired resistance to the thyroid hormone. The aim of this study was to investigate the effect of weight loss after bariatric surgery (BS) on resistance to thyroid hormones in patients with extreme obesity compared with a control group. We performed an observational study evaluating patients with extreme obesity who underwent BS. We included 106 patients (83 women) and 38 controls (24 women). The primary endpoint was the thyrotroph thyroxine resistance index (TT4RI) and thyroid stimulating hormone (TSH) index (TSHRI). The parameters were studied before and after surgery. TSHRI and TT4RI were higher in the obese patients than in the control group. TT4RI and TSHI decreased significantly over time after surgery, with this decrease being associated with the excessive body mass index (BMI) loss and C-reactive protein (CRP). In extreme obesity, BS promotes a significant decrease in the increased TT4RI and TSHI. This decrease of TT4RI and TSHI is progressive over time after BS and significantly associated with excess BMI lost and CRP. Extreme obesity is characterized by a mild reversible central resistance to thyroid hormones.

Beneficial Effects of Bariatric Surgery-Induced by Weight Loss on the Proteome of Abdominal Subcutaneous Adipose Tissue.

Bariatric surgery (BS) is the most effective treatment for obesity and has a positive impact on cardiometabolic risk and in the remission of type 2 diabetes. Following BS, the majority of fat mass is lost from the subcutaneous adipose tissue depot (SAT). However, the changes in this depot and functions and as well as its relative contribution to the beneficial effects of this surgery are still controversial. With the aim of studying altered proteins and molecular pathways in abdominal SAT (aSAT) after body weight normalization induced by BS, we carried out a proteomic approach sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis. These results were complemented by Western blot, electron microscopy and RT-qPCR. With all of the working tools mentioned, we confirmed that after BS, up-regulated proteins were associated with metabolism, the citric acid cycle and respiratory electron transport, triglyceride catabolism and metabolism, formation of ATP, pyruvate metabolism, glycolysis/gluconeogenesis and thermogenesis among others. In contrast, proteins with decreased values are part of the biological pathways related to the immune system. We also confirmed that obesity caused a significant decrease in mitochondrial density and coverage, which was corrected by BS. Together, these findings reveal specific molecular mechanisms, genes and proteins that improve adipose tissue function after BS characterized by lower inflammation, increased glucose uptake, higher insulin sensitivity, higher de novo lipogenesis, increased mitochondrial function and decreased adipocyte size.

Effect of Weight Loss after Bariatric Surgery on Thyroid-Stimulating Hormone Levels in Euthyroid Patients with Morbid Obesity.

Obesity is associated with several endocrine abnormalities, including thyroid dysfunction. The objective of this study was to investigate the effect of weight loss after bariatric surgery on thyroid-stimulating hormone (TSH) levels in euthyroid patients with morbid obesity. We performed an observational study, evaluating patients with morbid obesity submitted to bariatric surgery. We included 129 patients (92 women) and 31 controls (21 women). Clinical, anthropometric, biochemical, and hormonal parameters were evaluated. The primary endpoint was circulating TSH (µU/mL). Fasting TSH levels were higher in the obese group (3.3 ± 0.2) than in the control group (2.1 ± 0.2). The mean excessive body mass index (BMI) loss (EBMIL) 12 months after bariatric surgery was 72.7 ± 2.1%. TSH levels significantly decreased in the obese patients after surgery; 3.3 ± 0.2 vs. 2.1 ± 0.2 before and 12 months after surgery, respectively. Free thyroxine (T4) (ng/dL) levels significantly decreased in the obese patients after surgery; 1.47 ± 0.02 vs. 1.12 ± 0.02 before and 12 months after surgery, respectively. TSH decreased significantly over time, and the decrement was associated with the EBMIL. In euthyroid patients with morbid obesity, weight loss induced by bariatric surgery promotes a significant decline of the increased TSH levels. This decrement of TSH is progressive over time after surgery and significantly associated with excess BMI loss.