2018 Theses Doctoral
Pathways for kidney triglyceride accumulation
Lipid accumulation is a pathological feature of every type of kidney injury. However, despite this striking histological feature, physiological accumulation of lipids in the kidney is poorly understood. We studied whether the accumulation of lipids in the fasted kidney is derived from lipoproteins or non-esterified fatty acids (NEFAs). Increasing circulating NEFAs using a beta adrenergic receptor agonist caused a 15-fold greater accumulation of lipid in the kidney, while mice with reduced NEFAs due to adipose tissue deficiency of adipose triglyceride lipase had reduced renal triglycerides. Fasting-induced kidney lipid accumulation was not affected by inhibition of lipoprotein lipase (LpL) with poloxamer 407 or by use of mice with induced genetic LpL deletion. Despite the increase in CD36 expression with fasting, genetic loss of CD36 did not alter fatty acid uptake or triglyceride accumulation. Our data demonstrate that fasting-induced triglyceride accumulation in the kidney correlates with the plasma concentrations of NEFAs but is not due to uptake of lipoprotein lipids and does not involve the fatty acid transporter CD36. A second project was initiated to assess how diabetes causes increased systemic inflammation. Calgranulins S100A8 and S100A9 circulating levels are increased during diabetes and might instigate a sterile inflammatory response in the innate immune system. To determine whether krüppel-like factor 5 (KLF5) regulates S100A8 and S100A9 during hyperglycemia; we generated myeloid-specific KLF5 knockout mice (MKK) and found these mice had no change in circulating monocytes and neutrophils. We isolated neutrophils from these mice and found that S100A8 and S100A9 expression was not changed. We found similar null results when these mice were made diabetic. We conclude that this line of myeloid-deficient KLF5 knockout mice do not have changes in S100A8 or S100A9 expression or in the numbers of circulating white cells.
- Scerbo_columbia_0054D_14311.pdf application/pdf 3.31 MB Download File
- Academic Units
- Nutritional and Metabolic Biology
- Thesis Advisors
- Goldberg, Ira J.
- Ph.D., Columbia University