ABSTRACT
Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity.
Subject(s)
Adipose Tissue/physiology , Bariatric Surgery , Obesity/surgery , Adipocytes/metabolism , Adipokines/blood , Adipokines/metabolism , Animals , Catecholamines/blood , Disease Models, Animal , Humans , Inflammation , Insulin/blood , Insulin ResistanceABSTRACT
To investigate the function of the major non-muscle dystrophin isoform, Dp71, we substituted a beta-galactosidase (betagal) reporter gene for Dp71 by homologous recombination in embryonic stem cells. Staining for betagal activity in chimeric mice revealed Dp71 promoter activity in glial cells in the CNS, in neurons of the inner nuclear and inner plexiform layers of the retina, and in the kidney tubules and collecting ducts. Our observations demonstrate that Dp71 is widely expressed in the adult CNS (retina, cerebellum, cerebral cortex, ependyma, and choroid) as well as the adult kidney epithelium and suggest a broad function for Dp71 in differentiated tissues.
Subject(s)
Dystrophin/analogs & derivatives , Gene Expression Regulation/physiology , Gene Targeting , Protein Isoforms/genetics , beta-Galactosidase/genetics , Animals , Brain/metabolism , Chimera , Dystrophin/genetics , Evaluation Studies as Topic , Genes, Reporter , In Situ Hybridization , Mice , Mice, Inbred C57BL , Molecular WeightABSTRACT
Utrophin is a 400 kDa autosomal homolog of dystrophin and a component of the submembranous cytoskeleton. While multiple dystrophin isoforms have been identified along with alternatively spliced products, to date only two different mRNA species of utrophin have been identified. To determine the degree of evolutionary conservation between dystrophin and utrophin isoforms, we have compared their expression patterns in adult mice. Northern blot analysis of multiple adult tissues confirmed that only two major sizes of transcripts are produced from each gene: 13 and 5.5 kb from utrophin and 14 and 4.8 kb from dystrophin. However, western blot analysis detected several putative short utrophin isoforms that may be homologs of the dystrophin isoforms Dp140, Dp116 and Dp71. We also identified an alternatively spliced utrophin transcript that lacks the equivalent of the alternatively spliced dystrophin exon 71. Finally, we demonstrated that the C-terminal domain of utrophin targeted to neuromuscular junctions in normal mice, but localized to the sarcolemma efficiently only in the absence of dystrophin. Our results provide further evidence for a common evolutionary origin of the utrophin and dystrophin genes.
Subject(s)
Cytoskeletal Proteins/genetics , Dystrophin/genetics , Membrane Proteins/genetics , Alternative Splicing , Animals , Blotting, Northern , Gene Expression , Male , Mice , Mice, Inbred C57BL , Muscle, Skeletal/chemistry , Muscle, Skeletal/metabolism , RNA/genetics , RNA/metabolism , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/genetics , Tissue Distribution , UtrophinABSTRACT
Recent studies have begun to elucidate the localization of ion channels and receptors in central nervous system synapses. A family of proteins containing PDZ domains has been suggested to play essential roles in these processes. PSD-95 and chapsyn-110 have been implicated in the clustering of Shaker K+ channels and NMDA receptors in the mammalian brain, and Dlg plays a role in the clustering of Shaker K+ channels at the Drosophila neuromuscular junction (NMJ). We have explored whether Dlg might participate in mammalian NMJ organization. We demonstrate that Dlg is expressed in muscle and co-localizes with utrophin at the post-synaptic face of the mammalian NMJ. Dlg may therefore be important for establishing or maintaining the organization of protein complexes at the mammalian NMJ.
