Increased Autophagy and Apoptosis in the Kidneys of Intrauterine Growth Restricted Rats.

BACKGROUND: IUGR has been associated with nephron loss and chronic kidney disease (CKD). MATERIALS AND METHODS: We examined autophagy and apoptosis markers in the kidneys of IUGR Sprague Dawley rats induced by maternal low protein diet (LP), comparing them to controls. The autophagy marker LC3B, the pro-apoptotic protein Bax, and the anti-apoptotic protein Bcl-2 were determined by quantitative immunoblotting. Immunohistochemical expressions of LC3B, Bax, and Bcl-2 were evaluated at 4 weeks age. Glomerular counts (by maceration techniques) were performed at 5 weeks. RESULTS: The LP diet offspring were lighter (P < 0.05). In IUGR kidneys, LC3B and Bax were increased at birth (p < 0.05, p < 0.001) and at 4 weeks (p < 0.0142, p < 0.0001), Bcl-2 was decreased at birth (p < 0.05), and there were less glomeruli (p < 0.01) at 5 weeks. CONCLUSIONS: Autophagy and apoptosis may have a role in IUGR associated decreased nephron number in Sprague rats.

Examination of carnitine palmitoyltransferase 1 abundance in white adipose tissue: implications in obesity research.

Carnitine palmitoyltransferase 1 (CPT1) is essential for the transport of long-chain fatty acids into the mitochondria for oxidation. Recently, it was reported that decreased CPT1b mRNA in adipose tissue was a contributing factor for obesity in rats. We therefore closely examined the expression level of Cpt1 in adipose tissue from mice, rats, and humans. Cpt1a is the predominate isoform in adipose tissue from all three species. Rat white adipose tissue has a moderate amount of Cpt1b mRNA, but it is very minor compared with Cpt1b expression in muscle. Total CPT1 activity in adipose tissue is also minor relative to other tissues. Both Cpt1a and Cpt1b mRNA were increased in gonadal fat but not inguinal fat by diet-induced obesity in mice. We also measured CPT1a and CPT1b expression in subcutaneous adipose tissue from human subjects with a wide range of body mass indexes (BMIs). Interestingly, CPT1a expression positively correlated with BMI (R = 0.46), but there was no correlation with CPT1b (R = 0.04). Our findings indicate that white adipose tissue fatty acid oxidation capacity is minor compared with that of metabolically active tissues. Furthermore, given the already low abundance of Cpt1b in white adipose tissue, it is unlikely that decreases in its expression can quantitatively decrease whole body energy expenditure enough to contribute to an obese phenotype.

Differences in synovial fibrosis relative to range of motion in knee osteoarthritis patients.

This study tests if differences exist in the severity of synovial fibrosis between patients undergoing total knee arthroplasty (TKA) for osteoarthritis (OA) to help explain disparate deficits in pre- and postoperative range of motion (ROM) between patient groups. 117 knee OA patients were grouped by women (n = 74) and men (n = 43) or those who self-reported as Black (n = 48) or White (n = 69). ROM was measured pre- and post-TKA. Condyles and synovium collected during TKA were scored histologically for OA severity and synovitis. Fibrosis was measured from picrosirius-stained sections of the synovium. Data were analyzed using Mann-Whitney, parametric, and Spearman's rho tests with alpha at 0.05. We found no significant differences between patient age, BMI, radiographic scores, or deformity type when grouped by sex or race, or between metrics or OA severity when grouped by sex. Notably, higher synovitis was measured in women (p = .039) than men. White patients had greater ROM before (p = 0.46) and after surgery (p = .021) relative to Black patients. Fibrosis, but not OA severity and synovitis scores, for the total patient sample negatively correlated with preoperative (r s = -0.330; p = .0003) but not postoperative (rs = -0.032; p = .7627) ROM. Black patients manifested more fibrosis than White patients (p = <.0001), without significant differences between sexes. Statement of Clinical Significance: Coupled with histological scoring, measuring perioperative differences in synovial fibrosis against ROM may refine OA classification and justify the in-depth preoperative assessment of the knee as a whole. Such individualized analyses could guide personalized strategies to relieve symptomatic OA when TKA is not readily accessible and promote equitable TKA outcomes.