西亚试剂：LRP5 Regulates Human Body Fat Distribution

 Consistent with epidemiologic findings, physiological studies have shown that the gluteofemoral white adipose tissue (WAT) depot displays differential fatty acid (FA) handling compared to the subcutaneous (SC) abdominal WAT depot (Jensen, 2008 and Karpe and Pinnick, 2014). By favoring the long-term storage of FAs, gluteofemoral fat may protect skeletal muscle from ectopic lipid accumulation and lipotoxicity, which triggers insulin resistance (Schenk et al., 2008). Gluteofemoral fat may also contribute to improved metabolic risk by secreting a more beneficial adipocytokine profile than SC abdominal and visceral fat (Fontana et al., 2007 and Turer et al., 2011). Adipose-derived hormones and cytokines directly modulate systemic insulin sensitivity (Qatanani and Lazar, 2007).

WAT expands by an increase in adipocyte number (hyperplasia) and size (hypertrophy) (Spalding et al., 2008 and Tchoukalova et al., 2010). Adipocytes derive from mesenchymal stem cells (MSCs) and preadipocytes that reside in the stromovascular fraction of WAT. Several clinical and experimental studies indicate that discrete fat depots arise from distinct precursors with inherently different proliferative and adipogenic properties (Billon and Dani, 2012, Semple et al., 2011 and Tchkonia et al., 2006). It is further postulated that developmental pathways play a key role in establishing the distinct identities of adipose progenitors from separate locations and thus in determining (1) the relative size of fat depots, by determining adipocyte number (and size) within each depot, and (2) the function of WAT depots, by modulating expression of adipogenic genes and their downstream targets. Consistent with this hypothesis, stromovascular cells (SVCs) isolated from discrete fat depots exhibit distinct developmental gene expression profiles (Gesta et al., 2006 and Tchkonia et al., 2007). Furthermore, in a genome-wide association study (GWAS) meta-analysis, 4 of the 13 identified loci associated with body mass index (BMI)-adjusted waist-to-hip ratio (WHR), a measure of body fat distribution, mapped in or near developmental genes (Heid et al., 2010). Notably two of these, RSPO3 and ZNRF3

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