Differentiation of adipocytes in relation to acquired and congenital lipodystrophies

Differentiation of adipocytes, demonstrating gene activation and signaling pathways, in relation to acquired lipodystrophies: lipodystrophy genes and their associated protein products are bolded. Mesenchymal stem cells have the pluripotent ability to differentiate into osteocytes, myocytes, chondrocytes, stromal cells, or adipocytes. Wnt signal transduction pathways and other transcription factors lead to the development of a committed pre-adipocyte. Subsequently, adipogenic stimuli, such as insulin, glucocorticoids, IGF-1, and prostaglandins, initiate cell changes to differentiate into an adipocyte. Current data suggests that the BSCL-2 gene, coding for seipin, and AKT-2 play a role in adipocyte differentiation, and their mutations are involved in congenital generalized lipodystrophy (CGL) 2 and familial partial lipodystrophy (FPLD) 4, respectively. CCAAT-enhancer-binding proteins (C-EBP) b/d transcription factors stimulate factors PPARg, C-EBPa, and sterol regulatory element-binding protein (SREBP)1c, which are upregulated in this process; PPARg mutations are associated with FPLD3. Intracellular lipid accumulation in an adipocyte is dependent on substrate availability. In response to a variety of lipogenic signals, an adipocyte matures as the size of the lipid droplets are increased. Fatty acid synthase (FAS), acetyl coenzyme A carboxylase, and diacylglycerol acyltransferase (DGAT) expression is upregulated, necessary for the biosynthesis of phospholipids and triglycerides. AGPAT2 is responsible for acylating phosphatidic acid to synthesize triglycerides and phospholipids, and its mutation is involved in CGL1. PTRF regulates caveolae intracellularly and its functional loss results in CGL4. Apoptosis of adipocytes is influenced by LMNA, encoding for nuclear lamina proteins, and ZMPSTE24 required for post-translational lamina processing. Mutations in these genes lead to mandibuloacral dysplasia via premature nucleus disruption.