Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy

Amelioration of Diabetic Nephropathy Using a Retinoic Acid Receptorβ2 Agonist

“…The patterns of renal lipid accumulation in the HFD-fed cohort ( Figure 2A [b, yellow arrows]); are in agreement with those observed in human DN (Bobulescu et al, 2014;Herman-Edelstein et al, 2014) and murine diet-induced models of T2D (Bobulescu, 2010), with the appearance of tubule epithelial cell (TEC) vacuolization, a marker of cytosolic lipid droplets (LD) and impaired TEC lipid metabolism (Tervaert et al, 2010;Kang et al, 2015). We detected a 2.5-3.0 degree higher TEC vacuolization in HFD-fed mice compared to controls ( …”

“…hypothesis of DN (reviewed in (Bobulescu, 2010;Herman-Edelstein et al, 2014)), is supported by convincing evidence that ectopic renal LDs can initiate renal inflammatory and fibrotic responses which contribute to podocyte injury and loss (Bobulescu, 2010;Herman-Edelstein et al, 2014). Thus, the concomitant lower LD accumulation and decreases in effacement and injury in podocytes and ECs in HFD+AC261 treated mice compared to HFD-fed mice may be mechanistically related as podocytes and ECs synthesize and maintain components of the protein meshwork of the glomerular basement membrane (Abrahamson, 2012).…”

“…The final version may differ from this version. (Bobulescu et al, 2014;Herman-Edelstein et al, 2014), and as such, the "lipotoxicity"…”

Tissue-specific metabolic reprogramming drives nutrient flux in diabetic complications

“…Gene expression data also fit this pattern, as the expression of several genes involved in lipid metabolism was decreased in advanced DKD (61) and was strongly correlated with GFR, suggesting expression may decline with kidney function (62). It is likely that samples from advanced DKD subjects reflected the extensive tubular damage that is characteristic of that stage of the disease process, whereas those in early DKD patients reflect the increased metabolic activity of proximal tubular cells.…”

G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and Diabetes

“…Candidate gene expression was analyzed by real-time RT-PCR, performed as described previously, 61 using the TaqMan and SYBR system based on real-time detection of accumulated fluorescence (ABI Prism Step One; PerkinElmer, Foster City, CA). Fluorescence for each cycle was quantitatively analyzed by an ABI Step One sequence detection system (PerkinElmer).…”