Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...

Brown Adipose Tissue: Function and Physiological Significance

Steatohepatitis: a tale of two "hits"?

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.20466

Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity

Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine kinase found in all eukaryotes. The enzyme is a key regulator of numerous signalling pathways, including cellular responses to Wnt, receptor tyrosine kinases and G-protein-coupled receptors and is involved in a wide range of cellular processes, ranging from glycogen metabolism to cell cycle regulation and proliferation. GSK-3 is unusual in that it is normally active in cells and is primarily regulated through inhibition of its activity. Another peculiarity compared with other protein kinases is its preference for primed substrates, that is, substrates previously phosphorylated by another kinase. Several recent advances have improved our understanding of GSK-3 regulation in multiple pathways. These include the solution of the crystal structure of GSK-3, which has provided insight into GSK-3's penchant for primed substrates and the regulation of GSK-3 by serine phosphorylation, and findings related to the involvement of GSK-3 in the Wnt/beta-catenin and Hedgehog pathways. Finally, since increased GSK-3 activity may be linked to pathology in diseases such as Alzheimer's disease and non-insulin-dependent diabetes mellitus, several new GSK-3 inhibitors, such as the aloisines, the paullones and the maleimides, have been developed. Although they are just starting to be characterized in cell culture experiments, these new inhibitors hold promise as therapeutic agents.

GSK-3: tricks of the trade for a multi-tasking kinase.

Glycogen synthase kinase 3 (GSK3) was initially described as a key enzyme involved in glycogen metabolism, but is now known to regulate a diverse array of cell functions. The study of the substrate specificity and regulation of GSK3 activity has been important in the quest for therapeutic intervention.

The renaissance of GSK3.

Although described initially as an intracellular adipocyte-specific triacylglycerol lipase, it is now clear that HSL (hormone-sensitive lipase) is expressed in multiple tissues and plays a number of roles in lipid metabolism, including that of a neutral cholesteryl ester hydrolase The major isoform is a single polypeptide with a moleclar mass of approx 84 kDa and which comprises three major domains: a catalytic domain, a regulatory domain encoding several phosphorylation sites and an N-terminal domain involved in protein–protein and protein–lipid interactions The activity of HSL is regulated acutely by several mechanisms, including reversible phosphorylation by a number of different protein kinases, translocation to different sites within the cell and interaction with a number of proteins, some of which may serve to direct the inhibitory products of HSL away from the protein It is also apparent from work with HSL null mice that more than one enzyme species may be classified as a hormone-sensitive lipase The possible presence of HSL in macrophages remains controversial, and the role of the protein in pancreatic β-cells has yet to be fully elucidated Altered expression of HSL in different cell types may be associated with a number of pathological states, including obesity, atherosclerosis and Type II diabetes

/pdf/hormone-sensitive-lipase-new-roles-for-an-old-enzyme-164gh6a1l2.pdf

Hormone-sensitive lipase - new roles for an old enzyme

Translocation of hormone-sensitive lipase and perilipin upon lipolytic stimulation of rat adipocytes.

Regulation of Glycogen Synthesis by Amino Acids in Cultured Human Muscle Cells

Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by immune-mediated destruction of the biliary epithelial cells (BEC) lining the intrahepatic bile ducts (non-suppurative destructive cholangitis (NSDC)). Autoantibody and autoreactive T-cell responses specific for the self-antigen pyruvate dehydrogenase complex (PDC) are almost ubiquitous in PBC patients, leading to the view that the disease has an autoimmune aetiology. Autoreactive responses in PBC appear to be directed at the E2 and at the E3-binding protein (E3BP) (protein X) components of PDC, with the dominant B-cell and T-cell epitopes in E2 (fewer data are available for E3BP) spanning the inner (of two) lipoic acid-binding domains. The causal link between the breakdown of self-tolerance to PDC (particularly at the T-cell level) and the development of NSDC has been emphasised by the demonstration, in a murine model (experimental autoimmune cholangitis), that sensitisation with PDC of mammalian origin results in a breakdown of both B-cell and T-cell tolerance to murine PDC accompanied by the development of NSDC. An increasing understanding of the role played by PDC-specific autoreactive T cells in the pathogenesis of PBC has led us to examine the role played by the target cells in PBC (BEC) in both the inducer and effector mechanisms responsible for PBC.

Autoreactive responses to pyruvate dehydrogenase complex in the pathogenesis of primary biliary cirrhosis.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2888%2980799-3

Stephen J. Yeaman

Papers

Hormone-sensitive lipase - new roles for an old enzyme

Translocation of hormone-sensitive lipase and perilipin upon lipolytic stimulation of rat adipocytes.

Regulation of Glycogen Synthesis by Amino Acids in Cultured Human Muscle Cells

Autoreactive responses to pyruvate dehydrogenase complex in the pathogenesis of primary biliary cirrhosis.

Primary structure of the site on bovine hormone-sensitive lipase phosphorylated by cyclic AMP-dependent protein kinase.