Impairment of endothelial nitric oxide synthase causes abnormal fat and glycogen deposition in liver

Nitric oxide (NO) affects fatty acid synthesis and biogenesis of fatty acid consuming mitochondria. However, whether NO generated by the endothelial NO synthase isoform (eNOS) has significant impact on the synthesis and deposition of fat in liver remained unclear. We analyzed the quantity and distribution of mitochondria and fat in liver of wild-type (WT) mice and mice lacking eNOS (eNOS-KO). The livers of eNOS-KO mice contained tenfold more fat close (zone 1) and twenty fold more distal (zone 3) to the artery. The fat was deposited as droplets co-localized with mitochondria. Additionally, the livers of eNOS-KO mice contained 1.5-fold more homogenously distributed glycogen. No difference in the quantity of mitochondria was found between liver homogenates of eNOS-KO mice and WT animals. Mitochondria from liver homogenates of eNOS-KO mice exhibited a higher ratio of citrate synthase (CS) and NADH-cytochrome c oxidoreductase (KI+III) activity. We conclude that lack of eNOS-derived NO stimulates citrate- and lipid synthesis in liver thus contributing to the development of overweight. In support of this view, more visceral fat and 70% higher body weight was determined in one year old eNOS-KO mice in comparison to WT animals.     

Bovine gene polymorphisms related to fat deposition and meat tenderness

Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP), thyroglobulin (TG) and diacylglycerol O-acyltransferase (DGAT1). A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus), Canchim (5/8 Bos taurus + 3/8 Bos indicus), Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus), Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus) and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus) breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM) procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus.     

High visceral fat mass and high liver fat are associated with resistance to lifestyle intervention

Objective: High visceral adipose tissue (VAT) and high liver fat (LF) are associated with the metabolic syndrome and diabetes. We studied changes in these two fat depots during weight loss and analyzed whether VAT and LF at baseline predict the response to lifestyle intervention. Research Methods and Procedures: One hundred twelve subjects (48 men and 64 women; age, 46 ± 11 years; BMI, 29.2 ± 4.4 kg/m²) were studied after a follow up‐time of 264 ± 60 (SD) days. Insulin sensitivity was estimated from the oral glucose tolerance test. Body fat depots were quantified using magnetic resonance imaging and spectroscopy. Results: Cross‐sectionally high VAT (r = ?0.22, p = 0.02) and high LF (r = ?0.36, p < 0.0001) were independently associated with low insulin sensitivity. With intervention, BMI (?3.0%), VAT (?12.0%), and LF (?33.0%) were reduced (all p < 0.001). Insulin sensitivity was improved (+17%, p < 0.01). The changes in BMI (r = ?0.41), VAT (r = ?0.28), and LF (r = ?0.39) were associated with the increase in insulin sensitivity (all p < 0.01). High VAT (r = ?0.28, p = 0.01) and high LF (r = ?0.38, p < 0.01) at baseline were associated with a lesser increase in insulin sensitivity. Discussion: Baseline values and changes in BMI, VAT, and LF are related to changes in insulin sensitivity during lifestyle intervention. Subjects with high VAT and LF have a lower chance of profiting from lifestyle intervention and may require intensified lifestyle prevention strategies or even pharmacological approaches to improve insulin sensitivity.     

Quantitative and molecular genetic determination of protein and fat deposition

After 30 years of selection, breeding of the pig breed sus scrofa Piétrain has resulted in reduced backfat thickness (from 3.2 to 1.9 mm) and increased loin muscle area (40 to 60 cm2) which indicates high genetic determination of these body composition traits. The use of sophisticated quantitative genetic methods that include all genetic relationships of large populations has led to a high response to selection of these traits. Selection on feed intake, lean and fat tissue growth using nonlinear functions to optimise these traits during the entire growth period in a biological model offers the opportunity to further improve total genetic potential. Protein and lipid deposition rates during the entire growth period have to be known for this biological model to be applied; thus knowledge of the genetic background of these traits is of high economic value. With the use of molecular genetic methods, such as candidate gene and genome scan approaches, the identification of genes for obesity and growth can be obtained. In sus scrofa, candidate genes associated with obesity and growth include Leptin Receptor, Melanocortin-4 Receptor, Agouti related protein, Heart fatty acid binding protein 3, and Insulin-like growth factor 2. Some of these candidate genes also explain variation in obesity levels in humans. Initial genome-wide scans have identified quantitative trait loci (QTL) on chromosomes 1, 4, 5, 7 and X for obesity and on chromosomes 1, 4, 7, 8, 13 and 18 for growth. Physiological candidate genes and predispositional QTL for obesity are not always located on the same chromosome; this is known the "polygenic paradox". Use of a nonlinear growth function is recommended in order to give more insight into the physiological regulation of obesity traits. Sus scrofa is an excellent model organism to examine the genetic regulation of obesity. The conservation of DNA sequence and chromosomal segments between sus scrofa and homo sapiens will permit easy transfer of results to human studies.     

Interferon-gamma can augment expression ability of HLA-DR antigens on pokeweed mitogen-stimulated human T lymphocytes

The effect of natural interferon (IFN)-gamma on HLA-DR molecule expression of pokeweed mitogen (PWM)-stimulated T cells from cord blood and adult peripheral blood was assessed by direct immunofluorescence with fluorescein-labeled monoclonal anti-HLA-DR antibody on a flow cytometer. Although cord blood T cells showed only weak expression of HLA-DR antigens on PWM stimulation, IFN-gamma could enhance HLA-DR expression of PWM-stimulated cord blood T cells to levels comparable to those of adult ones. A similar, but slight, increase in HLA-DR expression was inducible in PWM-stimulated adult T cells by the addition of IFN-gamma, but at higher doses. This increased expression of HLA-Dr antigens on PWM-stimulated T cells was almost completely abolished by both acid treatment of IFN-gamma and neutralization of IFN-gamma with specific antiserum. In contrast to IFN-gamma, neither recombinant IFN-alpha nor IFN-beta showed any effect on HLA-DR expression of PWM-stimulated T cells. These results suggested a possible function of IFN-gamma that might modulate HLA-DR expression ability of T cells in their activation process.