Regulatory mechanisms of the early phase of white adipocyte differentiation: an overview.

The adipose organ comprises two main fat depots termed white and brown adipose tissues. Adipogenesis is a process leading to newly differentiated adipocytes starting from precursor cells, which requires the contribution of many cellular activities at the genome, transcriptome, proteome, and metabolome levels. The adipogenic program is accomplished through two sequential phases; the first includes events favoring the commitment of adipose tissue stem cells/precursors to preadipocytes, while the second involves mechanisms that allow the achievement of full adipocyte differentiation. While there is a very large literature about the mechanisms involved in terminal adipogenesis, little is known about the first stage of this process. Growing interest in this field is due to the recent identification of adipose tissue precursors, which include a heterogenous cell population within different types of adipose tissue as well as within the same fat depot. In addition, the alteration of the heterogeneity of adipose tissue stem cells and of the mechanisms involved in their commitment have been linked to adipose tissue development defects and hence to the onset/progression of metabolic diseases, such as obesity. For this reason, the characterization of early adipogenic events is crucial to understand the etiology and the evolution of adipogenesis-related pathologies, and to explore the adipose tissue precursors' potential as future tools for precision medicine.

The untargeted lipidomic profile of quarter milk from dairy cows with subclinical intramammary infection by non-aureus staphylococci.

This observational study determined the lipidome of cow milk during subclinical intramammary infection (IMI) by non-aureus staphylococci (NAS), also defined as coagulase-negative staphylococci, using an untargeted approach. Among the pathogens causing bovine IMI, NAS have become the most frequently isolated bacteria from milk samples. Although the application of system biology approaches to mastitis has provided pivotal information by investigating the transcriptome, proteome, peptidome, and metabolome, the milk lipidome during mammary gland inflammation remains undisclosed. To cover this gap, we determined the milk lipidome of 17 dairy cows with IMI caused by NAS (NAS-IMI), and we compared the results with those of healthy quarter milk from 11 cows. The lipidome was determined following a liquid chromatography-quadrupole time-of-flight mass spectrometry approach. Sixteen subclasses of lipids were identified in both groups of animals. From 2,556 measured lipids, the abundance of 597 changed more than 10-fold in quarter milk with NAS-IMI compared with healthy quarters. The results demonstrate the influence of NAS-IMI on the milk lipidome, implying significant changes in lipid species belonging to the family of triacylglycerols and sphingomyelins, and contribute to the understanding of inflammatory processes in the bovine udder, highlighting potential novel biomarkers for improving mastitis diagnostics.

Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity.

Lactate sits at the crossroad of metabolism, immunity, and inflammation. The expression of cellular lactate transporter MCT1 (known as Slc16a1) increases during immune cell activation to cope with the metabolic reprogramming. We investigated the impact of MCT1 deficiency on CD8+ T cell function during obesity-related inflammatory conditions. The absence of MCT1 impaired CD8+ T cell proliferation with a shift of ATP production to mitochondrial oxidative phosphorylation. In Slc16a1 f/f Tcell cre mice fed a high-fat diet, a reduction in the number of CD8+ T cells, which infiltrated epididymal visceral adipose tissue (epiWAT) or subcutaneous adipose tissue, was observed. Adipose tissue weight and adipocyte area were significantly reduced together with downregulation of adipogenic genes only in the epiWAT. Our findings highlight a distinct effect of MCT1 deficiency in CD8+ T cells in the crosstalk with adipocytes and reinforce the concept that targeting immunometabolic reprogramming in lymphocyte could impact the immune-adipose tissue axis in obesity.

[Determination of hepatic blood flow in chronic liver diseases using the constant infusion technic]. / Determinación del flujo sanguíneo hepático en hepatopatías crónicas con técnica de infusión contínua.

Hepatic blood flow was measured in 10 cirrhotic patients by a constant infusion of Indocyanine Green (ICG) and details of the technique are analysed. A decrease in total hepatic blood flow (0.777 +/- 0.38 l/min.) was found in most of the patients. Different variations in hepatic blood flow were observed in three patients after the administration of Cimetidine (300 mg IV). The response in hepatic blood flow in another patient in whom a peritoneo-jugular valve (Le Veen shunt) was inserted in analysed.

Acute and chronic hemodynamic effects of propranolol in unselected cirrhotic patients.

Different and contradictory results concerning the use of propranolol in the treatment of portal hypertension have been reported. This study was designed to investigate the hemodynamic effects of short- and long-term administration of propranolol in portal hypertensive patients. Portal pressure, cardiac index, heart rate and blood pressure were obtained in 18 unselected alcoholic cirrhotic patients with esophageal varices before and 60 min after the oral administration of 40 mg propranolol and again after 106 +/- 35 days of continuous oral administration (mean dose = 158 +/- 63 mg per day). Baseline portal pressure was 21.7 +/- 7.2 mm Hg. It decreased after 60 min to 17.2 +/- 5.5 mm Hg (p less than 0.01) and after long-term administration of propranolol to 16.1 +/- 5.7 mm Hg (p less than 0.01). No decrease in portal pressure was noted in 9 of 18 (50%) patients after acute administration and 5 of 17 (30%) patients after long-term administration. Baseline cardiac index was 5.1 +/- 1.2 liters X min-1 X m-2. It decreased after 60 min to 3.9 +/- 1.4 liters X min-1 X m-2 (p less than 0.01) and to 3.6 +/- 1.0 liters X min-1 X m-2 after long-term administration (p less than 0.001). Baseline heart rate was 85 +/- 11 beats per min. It decreased after 60 min to 75 +/- 9 (p less than 0.001) and after long-term administration to 62 +/- 6 (p less than 0.001) beats per min. Baseline mean arterial pressure was 108 +/- 11 Hg. It decreased after 60 min to 97 +/- 14 mm Hg (p less than 0.01) and after long-term administration to 103 +/- 14 mm Hg (not statistically significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of hepatic venous pressure gradient measurements in alcoholic cirrhosis: a 10-year prospective study.

BACKGROUND & AIMS: Different parameters are considered predictors of bleeding and death in alcoholic cirrhosis. The aim of this study was to establish the prognostic value of a prospective and sequential evaluation of portal pressure, variceal size, and Pugh's score in portal-hypertensive patients with alcoholic cirrhosis but no previous bleeding. METHODS: Thirty patients were evaluated for 42 +/- 5 months (median, 39 months). After baseline studies, 30 patients underwent an additional evaluation (follow-up 1; median, 10 months), 20 patients a second evaluation (follow-up 2; median, 25 months), and 13 patients a third evaluation (follow-up 3; median, 45 months). No prophylactic treatment for bleeding was given. End points were bleeding and/or death. RESULTS: Seventeen patients died, and 10 patients bled. At follow-up 1, portal pressure decreased both in survivors and nonbleeders (from 18.7 +/- 1.0 to 15.2 +/- 1.3 mm Hg [P < 0.01] and from 18.9 +/- 0.8 to 16.5 +/- 1.0 mm Hg [P < 0.05], respectively). On multivariate analysis (Cox model), portal pressure at follow-up 1 had the best prognostic and independent value for both bleeding and survival. Subsequent studies showed similar trends. CONCLUSIONS: Measurements of portal pressure provide unique prognostic information for predicting portal hypertensive-related bleeding and mortality in patients with alcoholic cirrhosis.

Determinacion del flujo sanguineo hepatico en hepatopatias cronicas con tecnica de infusion continua. / Determination of hepatic blood flow in chronic liver diseases by constant infusion technic

La determinacion del flujo sanguineo hepatico fue efectuada en pacientes portadores de hepatopatia cronica. Se utilizo um metodo de infusion continua con verde de indocianina, cuya tecnica se detalla.Los resultados basales en 10 pacientes y ejemplos de aplicacion de la tecnica son analizados. La correlacion del flujo sanguineo hepatico con otros elementos contribuye a definir de mejor manera el perfil hemodimico de las hepatopatias cronicas