Low miR-222 expression in human visceral adipose tissue is associated with insulin resistance and PTEN and p53 mRNA levels.

INTRODUCTION: The aim of this is study was to analyse the expression of miR-193b, miR-378, miR-Let7-d, and miR-222 in human visceral adipose tissue (VAT), as well as their association with obesity, insulin resistance (IR), and their role in the regulation of genes controlling adipose tissue homeostasis, including adipocytokines, the phosphatase and tension homologue (PTEN), and tumour protein 53 (p53). MATERIAL AND METHODS: VAT was obtained from normal-weight (NW), overweight, and obese (OW/OB) subjects with and without IR. Stem-loop RT-qPCR was used to evaluate miRNA expression levels. miRTarBase 4.0, miRWalk, and DIANA-TarBase v8 were used for prediction of validated target gene of the miRNA analysed. A qPCR was used to evaluate PTEN, p53, leptin (LEP), and adiponectin (ADIPOQ) mRNA. RESULTS: miR-222 was lower in IR subjects, and miR-222 and miR-378 negatively correlated with HOMA-IR. PTEN and p53 are miR-222 direct targets according to databases. mRNA expression of PTEN and p53 was lower in OW/OB subjects with and without IR, compared to NW group and its levels positively associated with miR-222. Additionally, p53 and PTEN are positively associated with serum leptin levels. On the other hand, miR-193b and miR-378 negatively correlated with serum leptin but not with mRNA levels. Moreover, miR-Let-7d negatively correlated with serum adiponectin but not with adiponectin mRNA levels. CONCLUSIONS: Lower miR-222 levels are associated with IR, and PTEN and p53 expression; the implication of these genes in adipose tissue homeostasis needs more research.

Low prolactin levels are associated with visceral adipocyte hypertrophy and insulin resistance in humans.

PURPOSE: Low prolactin (PRL) serum levels are associated with glucose intolerance and type 2 diabetes in adults, and with metabolic syndrome and obesity in children. In obese rodents, PRL treatment promotes insulin sensitivity by maintaining adipose tissue fitness, and lack of PRL signaling exacerbates obesity-derived metabolic alterations. Since adipose tissue dysfunction is a key factor triggering metabolic alterations, we evaluated whether PRL serum levels are associated with adipocyte hypertrophy (a marker of adipose tissue dysfunction), insulin resistance, and metabolic syndrome in lean, overweight, and obese adult men and women. METHODS: Samples of serum and adipose tissue from 40 subjects were obtained to evaluate insulin resistance index (homeostasis model assessment of insulin resistance (HOMA-IR)), signs of metabolic syndrome (glucose levels, high-density lipoproteins, triglycerides, blood pressure, and waist circumference), as well as adipocyte size and gene expression in fat. RESULTS: Lower PRL serum levels are associated with adipocyte hypertrophy, in visceral but not in subcutaneous fat, and with a higher HOMA-IR. Furthermore, low systemic PRL levels together with high waist circumference predict an elevated HOMA-IR whereas low serum PRL values in combination with high blood glucose predicts visceral adipocyte hypertrophy. In agreement, visceral fat from insulin resistant subjects shows reduced expression of prolactin receptor. However, there is no association between PRL levels and obesity or signs of metabolic syndrome. CONCLUSIONS: Our results support that low levels of PRL are markers of visceral fat dysfunction and insulin resistance, and suggest the potential therapeutic value of medications elevating PRL levels to help maintain metabolic homeostasis.

Secondary colonic necrosis. Case report.

BACKGROUND: Colonic vascular lesion secondary to verapamil overdose is mediated by free radicals, forming vascular microtrombos and endotoxin generation, being a difficult diagnosis. CLINICAL CASE: A 27-year-old female is admitted with an acute abdomen of 4 days after an event referred for a suicidal attempt due to an overdose of verapamil, operating surgically where there is a right transmural colon necrosis, performing a right hemicolectomy with terminal ileostomy. CONCLUSIONS: Recognize and properly treat an acute abdomen, not always reach an adequate diagnosis, so a thorough history could conclude.

ANTECEDENTES: La lesión vascular colónica secundaria a la sobredosis de verapamilo, es mediada por radicales libres, formando microtrombos vasculares y generación de endotoxinas, siendo un diagnostico difícil. CASO CLÍNICO: Femenino de 27 años, ingresa con abdomen agudo de 4 días posteriores a un evento remitido de intento suicida por sobredosis de verapamilo, interviniéndose quirúrgicamente donde se halla necrosis colónica transmural derecha, realizando hemicolectomía derecha con ileostomía terminal. CONCLUSIONES: Reconocer y tratar de forma adecuada un abdomen agudo, no siempre se suele llegar a un adecuado diagnostico, por lo cual una minuciosa anamnesis lograría concluirlo.

Prolactin Promotes Adipose Tissue Fitness and Insulin Sensitivity in Obese Males.

Excessive accumulation of body fat triggers insulin resistance and features of the metabolic syndrome. Recently, evidence has accumulated that obesity, type 2 diabetes, and metabolic syndrome are associated with reduced levels of serum prolactin (PRL) in humans and rodents, raising the question of whether low PRL levels contribute to metabolic dysfunction. Here, we have addressed this question by investigating the role of PRL in insulin sensitivity and adipose tissue fitness in obese rodents and humans. In diet-induced obese rats, treatment with PRL delivered via osmotic mini-pumps, improved insulin sensitivity, prevented adipocyte hypertrophy, and reduced inflammatory cytokine expression in visceral fat. PRL also induced increased expression of Pparg and Xbp1s in visceral adipose tissue and elevated circulating adiponectin levels. Conversely, PRL receptor null mice challenged with a high-fat diet developed greater insulin resistance, glucose intolerance, and increased adipocyte hypertrophy compared with wild-type mice. In humans, serum PRL values correlated positively with systemic adiponectin levels and were reduced in insulin-resistant patients. Furthermore, PRL circulating levels and PRL produced by adipose tissue correlated directly with the expression of PPARG, ADIPOQ, and GLUT4 in human visceral and sc adipose tissue. Thus, PRL, acting through its cognate receptors, promotes healthy adipose tissue function and systemic insulin sensitivity. Increasing the levels of PRL in the circulation may have therapeutic potential against obesity-induced metabolic diseases.