The heart has both the greatest caloric needs and the most robust oxidation of fatty acids. Under pathological conditions such as obesity and type 2 diabetes, cardiac uptake and oxidation are not balanced and hearts accumulate lipid potentially leading to cardiac lipotoxicity. We will first review the pathways utilized by the heart to acquire fatty acids from the circulation and to store triglyceride intracellularly. Then we will describe mouse models in which excess lipid accumulation causes heart dysfunction and experiments performed to alleviate this toxicity. Finally, the known relationships between heart lipid metabolism and dysfunction in humans will be summarized.

storage of energy as neutral lipid (i.e., triacylglycerol) in adipose tissues. Storing excess energy as neutral lipid is an evolutionarily conserved characteristic common to virtually all animals, providing a valuable energy source during periods of nutrient scarcity ( 2, 3 ). Vertebrates are capable of storing neutral lipid in several tissues, with adipose tissue serving as the primary depot. The principal cellular component of adipose tissue is the adipocyte, a cell type specialized for storing fat in cytoplasmic neutral lipid droplets and endocrine control of energy balance ( 4, 5 ).Current knowledge of adipocyte development and physiology is largely derived from research using mammalian model systems. Mammals develop two general types of adipose tissues: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is more abundant and serves primarily as a site of energy storage and mobilization, while BAT primarily functions in energy expenditure in the form of thermogenesis. WAT and BAT form in distinct anatomic depots during mammalian development, with different depots displaying distinctive patterns of gene expression, endocrine sensitivity, and association with metabolic diseases ( 2 ). Adipocytes within WAT (white adipocytes) and BAT (brown adipocytes) both contain cytoplasmic neutral lipid droplets; however, mature white adipocytes typically contain a single large droplet (unilocular), while brown adipocytes contain multiple smaller lipid droplets. Previous studies have indicated that adipocytes develop from multipotent mesenchymal stem cells (MSCs). MSCs are classically considered to be derived from the mesoderm, although recent studies suggest that MSCs have additional developmental origins, such as the neural crest or neuroepithelium ( 6, 7 ). In addition to producing adipocytes during development, MSCs are thought to populate distinct anatomical sites in adult animals, including bone The worldwide epidemic of obesity and associated complications, such as type II diabetes, hypertension, and cardiovascular disease, has resulted in the designation of obesity as a major public health challenge of our time ( 1 ). Obesity is a disorder of energy imbalance in which an excess of energy intake over expenditure leads to increased This work was funded

Background Cardiac dysfunction with sepsis is associated with both inflammation and reduced fatty acid oxidation (FAO). We hypothesized that energy deprivation accounts for sepsis-related cardiac dysfunction. Methods and Results E. coli lipopolysaccharide (LPS) administered to C57BL/6 mice (WT) induced cardiac dysfunction and reduced FAO and mRNA levels of peroxisome proliferator-activated receptor (PPAR) α and its downstream targets within 6-8h. Transgenic mice in which cardiomyocyte-specific expression of PPARγ is driven by the alpha myosin heavy chain promoter (αMHC-PPARγ) were protected from LPS-induced cardiac dysfunction. Despite a reduction in PPARα, FAO and associated genes were not decreased in hearts of LPS-treated αMHC-PPARγ mice. LPS treatment, however, continued to induce inflammation-related genes, such as interleukin (IL)-1α, IL-1β, IL-6 and tumor necrosis factor α in hearts of αMHC-PPARγ mice. Treatment of WT mice with LPS and the PPARγ agonist rosiglitazone, but not the PPARα agonist (WY-14643), increased FAO, prevented LPS-mediated reduction of mitochondria and treated cardiac dysfunction, as well as it improved survival despite continued increases in the expression of cardiac inflammatory markers. Conclusion Activation of PPARγ in LPS-treated mice prevented cardiac dysfunction and mortality despite development of cardiac inflammation and PPARα downregulation.

Background: Obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) are serious health concerns, especially in Western populations. Antibiotic exposure and high-fat diet (HFD) are important and modifiable factors that may contribute to these diseases.

Complex microbial communities reside within the intestines of humans and other vertebrates. Remarkably little is known about how these microbial consortia are established in various locations within the gut, how members of these consortia behave within their dynamic ecosystems, or what microbial factors mediate mutually beneficial host-microbial interactions. Using a gnotobiotic zebrafishPseudomonas aeruginosa model, we show that the transparency of this vertebrate species, coupled with methods for raising these animals under germ-free conditions can be used to monitor microbial movement and localization within the intestine in vivo and in real time. Germ-free zebrafish colonized with isogenic P. aeruginosa strains containing deletions of genes related to motility and pathogenesis revealed that loss of flagellar function results in attenuation of evolutionarily conserved host innate immune responses but not conserved nutrient responses. These results demonstrate the utility of gnotobiotic zebrafish in defining the behavior and localization of bacteria within the living vertebrate gut, identifying bacterial genes that affect these processes, and assessing the impact of these genes on host-microbial interactions.Danio rerio ͉ establishment of a gut microbiota ͉ flagellar motility ͉ host-microbial symbiosis and mutualism ͉ Pseudomonas aeruginosa