Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase

Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.     

Using gene expression noise to understand gene regulation

Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a major source of this variability, and its physiological consequences have been topics of intense research for the last decade. Several recent studies have measured variability in protein and messenger RNA levels, and they have discovered strong connections between noise and gene regulation mechanisms. When integrated with discrete stochastic models, measurements of cell-to-cell variability provide a sensitive "fingerprint" with which to explore fundamental questions of gene regulation. In this review, we highlight several studies that used gene expression variability to develop a quantitative understanding of the mechanisms and dynamics of gene regulation.     

An immunohistochemical study of the role of matrix metalloproteinases and their tissue inhibitors in chronic mitral valvular disease (valvular endocardiosis) in dogs

While the pathogenesis of chronic valvular disease (CVD) in dogs remains unclear, alterations in the activity of specific metalloproteinase enzymes and their inhibitors within the valve stroma are suspected of having a role. This study describes the immunohistochemical distribution pattern of matrix metalloproteinase (MMP) types 2, 9 and 14 and their tissue inhibitors, termed tissue inhibitors of metalloproteinase (TIMP), types 2 and 3, in normal canine mitral valves (MVs) (n=10) and in dogs with mild (n=7), moderate (n=14) and severe (n=9) CVD. In normal MVs, MMP-2 and -14, and TIMP-2 were expressed in isolated stromal cells. Tissue inhibitor of metalloproteinase-3 exhibited moderate intracellular and mild extracellular expression. With increasing severity of CVD, the expression of MMP-2 decreased. The number of stromal cells expressing MMP-14 increased, predominantly in the margins of the nodular lesions. Tissue inhibitor of metalloproteinase-2 and -3 expression increased both intra- and extracellularly. Matrix metalloproteinase-9 was not detected in normal or diseased valves. In conclusion, CVD was characterised by alterations in the distribution and intensity of valvular MMP and TIMP expression, suggesting that depressed catabolism and the accumulation of extracellular matrix components within affected valves contributes to their structural alteration and consequent loss of function.     

Estimates of prevalence of hip dysplasia in Golden Retrievers and Rottweilers and the influence of bias on published prevalence figures

OBJECTIVE: To estimate prevalence of canine hip dysplasia (CHD) in Golden Retrievers and Rottweilers and identify sources of bias in published reports. DESIGN: Prospective study. ANIMALS: 200 clinically normal Golden Retrievers and 140 clinically normal Rottweilers between 24 and 60 months of age referred for hip evaluation (group 1) and 93 clinically normal dogs evaluated for Orthopedic Foundation for Animals (OFA) hip certification (group 2). PROCEDURE: Hip-extended pelvic radiographs from group 1 dogs were screened for CHD. Radiographs were evaluated twice; the first interpretation used an OFA-type subjective 7-point scoring system, and the second included the caudolateral curvilinear osteophyte as an additional sign of degenerative joint disease. The OFA submission rate of group 2 dogs was determined from the number of official reports returned from the OFA. RESULTS: Prevalence of CHD in Golden Retrievers ranged from 53% to 73% and in Rottweilers ranged from 41% to 69%. Among dogs referred for OFA evaluation, radiographs from 49 (53%) were submitted to OFA. Of submitted radiographs, 45 (92%) were normal; of radiographs not submitted, 22 (50%) were normal. Radiographs with normal-appearing hips were 8.2 times as likely to be submitted to the OFA. Compared with Golden Retrievers, Rottweiler radiographs were significantly more likely to be submitted for OFA certification. CONCLUSIONS AND CLINICAL RELEVANCE: Prevalence of CHD in these 2 breeds may be much higher than previously reported in the United States. Results suggest substantial bias in the OFA database, which causes lower estimates of prevalence of CHD.     

The relationship between meal composition and long-term diet choice

When animals are offered a choice of feeds that are nutritionally complementary, they are able to select a consistent combination of these feeds over long periods of time. Analysis of how such consistent diet choice is achieved, in terms of short-term feeding behavior, may further our knowledge of how animals regulate nutrient intake. Previous work, on meal pattern analysis and on nutrient synchronization, led us to hypothesize that animals may select a consistent diet within a meal. In three experiments cows were offered a choice between high- (H) and low- (L) protein feeds and short-term feeding behavior data were collected using computerized feeders. Feeding behavior was first analyzed in terms of visit characteristics. A greater average daily intake of H, relative to L, was more closely related to the ratio of H visits to L visits than to differences in the intake per visit to feeders supplying H or L. Individual meal criteria were estimated using a mixed-distribution model, and visits were clustered into meals. Cows typically had approximately six meals per day. The observed frequency distribution of meal composition, in terms of the proportion of visits to H feeders, was determined. Subsequently, the observed visits were randomly reclustered into bouts consisting of the same number of visits as were observed in meals, and the frequency distribution of random bout composition was calculated. If frequency distributions of meals and random bouts coincide, then this is evidence that cows do not regulate diet choice within a meal. Comparison of the frequency distributions of meals and random bouts provided no evidence that cows attempted to achieve their long-term average diet composition within a meal. We also investigated whether cows tried to achieve a consistent diet choice within a meal by adjusting their intake per visit, depending on the feed type visited and the proportion of visits to H feeders in a meal. There was no evidence that this occurred. In conclusion, our analyses have shown that cows did not attempt to select within a meal a consistent diet in terms of protein to energy ratio. Indeed, our data and the literature suggest that the timeframe over which the intake of energy and protein is regulated must be greater than a meal in a number of animal species.