The beta-adrenergic receptors (beta-AR) are present on the surface of almost every type of mammalian cell. These receptors are stimulated physiologically by the neurotransmitter, norepinephrine and the adrenal medullary hormone, epinephrine. There are three subtypes of beta-AR, namely, beta1-AR, beta2-AR, and beta3-AR; the pharmacological and physiological responses of an individual cell result from the particular mixture of the three beta-AR subtypes present on that cell. Species-specific structure (amino acid sequence) also causes modification of the function of a given beta-AR subtype. Knowledge of the beta-AR subtypes present in various cell types, coupled with knowledge of receptor structure (sequence), will allow an understanding of the complexity of physiological function regulated by beta-AR. Oral administration of some beta-AR agonists increases muscle and decreases fat accretion in cattle, pigs, poultry, and sheep. The large number of physiological functions controlled by beta-AR suggests that the mechanism(s) for the observed changes in carcass composition may be extremely complex. Any proposed mechanism must begin with the possibility of direct effects of the agonist on skeletal muscle and adipocyte beta-AR. However, many other mechanisms, such as modification of blood flow, release of hormones, or central nervous system control of feed intake may contribute to the overall effects observed with a given beta-AR agonist in a given species. Furthermore, the pharmacodynamic properties of a particular agonist are complex and expected to vary among species as well as within the same species at different ages or when fed different diets.

The emerging obesity crisis and consequent concerns for corrective measures and appropriate public policy have stimulated research into causes, prevention, remediation, and health consequences of obesity and associated maladies. Such research areas include eating behavior, appetite control, and food intake regulation as well as the regulation of lipid metabolism, cardiovascular function, endocrine function, and dyslipidemia states utilizing various animal models and cell culture systems. Although the liver has a central role in lipid/fatty acid synthesis and glucose is the precursor for de novo fatty acid synthesis in rodents and humans, in many other species, adipose tissues are the primary sites of lipogenesis. In addition, many species utilize acetic acid as a precursor for fatty acid synthesis. This fundamental difference in the site of fatty acid synthesis and the pattern of consequent lipid trafficking influences overall animal lipid metabolism and the role of regulatory hormones and transcription factors. Researchers utilizing various animal species in targeted biomedical research should be aware of these species differences when interpreting their data. In addition, many animal species are used for food production, recreational, and companion purposes. Understanding the lipid metabolism regulatory mechanisms of such species from a comparative perspective is important for the proper nutrition and health of these animals.

. ICAM-1 expression in adipose tissue: effects of diet-induced obesity in mice.

Cardiac and skeletal muscle both respond to elevated fatty acid availability by increasing fatty acid oxidation, an effect mediated in large part by peroxisome proliferator-activated receptor-alpha (PPAR alpha). We hypothesized that cardiac and skeletal muscle alter their responsiveness to fatty acids over the course of the day, allowing optimal adaptation when availability of this substrate increases. In the current study, pyruvate dehydrogenase kinase 4 (pdk4) was utilized as a representative PPAR alpha-regulated gene. Opposing diurnal variations in pdk4 expression were observed in cardiac and skeletal muscle isolated from the ad libitum-fed rat; pdk4 expression peaked in the middle of the dark and light phases, respectively. Elevation of circulating fatty acid levels by high-fat feeding, fasting, and streptozotocin-induced diabetes increased pdk4 expression in both heart and soleus muscle. Highest levels of induction were observed during the dark phase, regardless of muscle type or intervention. Specific activation of PPAR alpha with WY-14643 rapidly induced pdk4 expression in heart and soleus muscle. Highest levels of induction were again observed during the dark phase. The same pattern of induction was observed for the PPAR alpha-regulated genes malonyl-CoA decarboxylase and uncoupling protein 3. Investigation into the potential mechanism(s) for these observations exposed a coordinated upregulation of transcriptional activators of the PPAR alpha system during the night, with a concomitant downregulation of transcriptional repressors in both muscle types. In conclusion, responsiveness of cardiac and skeletal muscle to fatty acids exhibits a marked diurnal variation. These observations have important physiological and pathophysiological implications, ranging from experimental design to pharmacological treatment of patients.

by acting in concert with uncoupling protein (UCP)3. We previously showed that ucp3 is a peroxisome proliferator-activated receptor-␣ (PPAR␣)-regulated gene, allowing induction when FA availability increases. On the assumption that UCP3 and MTE1 act in partnership to increase FAO, we hypothesized that mte1 is also a PPAR␣-regulated gene in cardiac and skeletal muscle. Using real-time RT-PCR, we characterized mte1 gene expression in rat heart and soleus muscles. Messenger RNA encoding for mte1 was 3.2-fold higher in heart than in soleus muscle. Cardiac mte1 mRNA exhibited modest diurnal variation, with 1.4-fold higher levels during dark phase. In contrast, skeletal muscle mte1 mRNA remained relatively constant over the course of the day. High-fat feeding, fasting, and streptozotocin-induced diabetes, interventions that increase FA availability, muscle PPAR␣ activity, and muscle FAO rates, increased mte1 mRNA in heart and soleus muscle. Conversely, pressure overload and hypoxia, interventions that decrease cardiac PPAR␣ activity and FAO rates, repressed cardiac mte1 expression.