Adipogenic potential of skeletal muscle satellite cells

Abstract

Lipases are acyl hydrolases that represent a diverse group of enzymes present in organisms ranging from prokaryotes to humans. This article focuses on an evolutionarily related family of extracellular lipases that include lipoprotein lipase, hepatic lipase and endothelial lipase. As newly synthesized proteins, these lipases undergo a series of co- and post-translational maturation steps occurring in the endoplasmic reticulum, including glycosylation and glycan processing, and protein folding and subunit assembly. This article identifies and discusses mechanisms that direct early and late events in lipase folding and assembly. Lipase maturation employs the two general chaperone systems operating in the endoplasmic reticulum, as well as a recently identified lipase-specific chaperone termed lipase maturation factor 1. We propose that the two general chaperone systems act in a coordinated manner early in lipase maturation in order to help create partially folded monomers; lipase maturation factor 1 then facilitates final monomer folding and subunit assembly into fully functional homodimers. Once maturation is complete, the lipases exit the endoplasmic reticulum and are secreted to extracellular sites, where they carry out a number of functions related to lipoprotein and lipid metabolism.

The ER-Associated Degradation Adaptor Protein Sel1L Regulates LPL Secretion and Lipid Metabolism

“…Thus, our findings may have therapeutic implications. Recent discovery of LMF1, GPIHBP1 and ANGPTL4 have provided key insights into LPL biology, where they play key roles at different stages of LPL maturation and function (Dijk and Kersten, 2014; Doolittle and Peterfy, 2010; Wang and Eckel, 2009). In this study, we have identified Sel1L as a modulator of LPL secretion from the ER.…”

“…LPL-mediated hydrolysis of dietary triglycerides packaged in chylomicrons is increased at adipose tissues during feeding (to increase lipid storage), but suppressed during fasting (Williams, 2008). Production of active LPL is tightly regulated at multiple stages (Dijk and Kersten, 2014; Doolittle and Peterfy, 2010; Wang and Eckel, 2009), one of which is in the ER. Various ER chaperones are required for the folding of nascent LPL polypeptides into properly folded dimeric state (Ben-Zeev et al, 1992; Ben-Zeev et al, 2002; Vannier and Ailhaud, 1989).…”

“…In the absence of LMF1, LPL forms aggregates, becomes transport-incompetent and retained in the ER (Peterfy et al, 2007). Defects in LPL maturation in the ER result in hypertriglyceridemia known as familial hyperchylomicronemia, which contribute to the development of heart diseases, metabolic syndrome and other diseases in humans (Doolittle and Peterfy, 2010). Despite decades of effort, the maturation and secretion processes of LPL in the ER remain poorly understood.…”

GPIHBP1 and Plasma Triglyceride Metabolism

“…LPL is generally thought to be a head-to-tail homodimer [42–44]; consequently, one might reasonably presume that LPL would have two binding sites for GPIHBP1. Thus far, however, no one has shown that this is the case.…”

Increased adipogenic conversion of muscle satellite cells in obese Zucker rats

“…5 SCs represent a heterogeneous stem-cell population, 6,7 characterized by plasticity [8][9][10] and self-renewal. 11,12 Although SCs are mostly considered as myogenic precursors, they also undergo adipogenic differentiation induced by adipogenic factors 8,9,13,14 and by spontaneous occurrence; 8,10 this ability is greater in SCs from oxidative muscles than in those from glycolytic muscles 15 and it is increased in SCs isolated from 23-month-old mice compared with 8-month-old mice. 16 Moreover, it is likely that the SC's fate could be influenced by pathological conditions, such as obesity and diabetes.…”