Accumulation of 4-Hydroxynonenal Characterizes Diabetic Fat and Modulates Adipogenic Differentiation of Adipose Precursor Cells.
Giuseppe MurdoloDesiree BartoliniCristina TortoioliCristiana VermigliMarta PiroddiFrancesco GalliPublished in: International journal of molecular sciences (2023)
Redox imbalance in fat tissue appears to be causative of impaired glucose homeostasis. This "proof-of-concept" study investigated whether the peroxidation by-product of polyunsaturated n-6 fatty acids, namely 4-hydroxynonenal (4-HNE), is formed by, and accumulates in, the adipose tissue (AT) of obese patients with type 2 diabetes (OBT2D) as compared with lean, nondiabetic control subjects (CTRL). Moreover, we studied the effects of 4-HNE on the cell viability and adipogenic differentiation of adipose-derived stem cells (ASCs). Protein-HNE adducts in subcutaneous abdominal AT (SCAAT) biopsies from seven OBT2D and seven CTRL subjects were assessed using Western blot. The effects of 4-HNE were then studied in primary cultures of ASCs, focusing on cell viability, adipogenic differentiation, and the "canonical" Wnt and MAPK signaling pathways. When compared with the controls, the OBT2D patients displayed increased HNE-protein adducts in the SCAAT. The exposure of ASCs to 4-HNE fostered ROS production and led to a time- and concentration-dependent decrease in cell viability. Notably, at concentrations that did not affect cell viability (1 μM), 4-HNE hampered adipogenic ASCs' differentiation through a timely-regulated activation of the Wnt/β-catenin, p38MAPK, ERK1/2- and JNK-mediated pathways. These "hypothesis-generating" data suggest that the increased accumulation of 4-HNE in the SCAAT of obese patients with type 2 diabetes may detrimentally affect adipose precursor cell differentiation, possibly contributing to the obesity-associated derangement of glucose homeostasis.
Keyphrases
- adipose tissue
- signaling pathway
- insulin resistance
- fatty acid
- induced apoptosis
- type diabetes
- cell proliferation
- metabolic syndrome
- weight loss
- end stage renal disease
- high fat diet
- cell death
- stem cells
- epithelial mesenchymal transition
- pi k akt
- ejection fraction
- chronic kidney disease
- blood glucose
- south africa
- oxidative stress
- bariatric surgery
- transcription factor
- protein protein
- blood pressure
- amino acid
- peritoneal dialysis
- high fat diet induced
- machine learning
- small molecule
- atomic force microscopy
- endoplasmic reticulum stress
- ultrasound guided
- physical activity
- glycemic control