(856.6) Obesity Exacerbates Lipid Nephrotoxicity and Renal Injury in a Model of Ovarian Hormone Deficiency

Poster Board Number: E121

Patrick Walsh (Des Moines University), Scott Johnson (Des Moines University), Woo Suk Kim (Des Moines University), Victor Babich (Mercy College of Health Sciences, Des Moines University), Maria Barnes (Des Moines University), Francesca Di Sole (Des Moines University)

Obesity rates are continually increasing both in the USA and around the world. As rates of obesity continue to grow, public health concerns remain a top priority in order to curtail mortality and morbidity. An increase in visceral adipose tissue is correlated with dysfunction in multiple organs, including the kidneys. Increases in basal metabolic index, or BMI, has been linked to increases in triglyceride accumulation in the kidneys. Obesity accounts for ~25% of kidney diseases observed in women; however, its effects on kidney function have not been defined in post-menopausal women. In an ovarian hormone deficient mouse model (ovariectomized animals), we measured a significant weight gain compared with sham-operated control, associated with perirenal adipose tissue accumulation, and an increase in 1. glomerular filtration rate (GFR) used to determine renal function, 2. protein level of the NGAL, an early biomarker of kidney injury and 3. intrarenal lipid accumulation found in the renal tubules. In this study, we aim to determine whether obesity affects the levels of renal injury and lipid accumulation measured in a model of ovarian hormone deficiency. We studied four groups of mice: the first and second groups underwent ovariectomy (OVX); group one was fed a 60% high-fat (HF) diet, and group two was on a 10% low-fat (LH) diet. The third and fourth groups (controls), underwent surgery without ovariectomy (SHAM) and were fed a HF or LF diet. All animals had ad libitum access to their respective diet for fourteen weeks (i.e., ten weeks prior to surgery and four weeks after). Significant increase in body weight was measured in mice on HF compared to LF diet. The size of triglyceride droplets in the renal tubules was significantly higher (20-25%) in OVX compared to SHAM-operated control mice on both HF and LF diets. The Neutrophil Gelatinase Associated Lipocalin (NGAL) protein levels were measured as a biomarker of kidney injury. Levels of NGAL protein expression increased in OVX mice when compared to SHAM control in the renal tubules of mice on both HF (211.3 ± 3.7%, plt;0.0001) and LF diet (111.33 ± 1.7%, p=0.02). In the glomeruli, NGAL protein expression levels increased in OVX mice compared to SHAM control in HF (188.8 ± 9.9%, plt;0.0001) and LF diet fed groups (113.1 ± 4.9%, p=0.64). Furthermore, mice on HF diet had significant higher NGAL levels in OVX and sham-control conditions than mice in the same conditions on LF diet. These findings indicate that weight gain exacerbates renal injury induced by OVX, and that estrogen may be protective against excessive accumulation of triglycerides in kidney structures. Our study supports the understanding of the mechanisms implicated in the development of kidney diseases in obese post-menopausal women.

This research was supported by DMU Iowa Osteopathic Education and Research Ramp;amp;G Award #03-20-09.