Kidney osteoclast factors and matrix metalloproteinase expression in a mice model of diet-induced obesity and diabetes

Abstract

The role of RANKL/RANK/OPG system on bone remodeling is well known, and there is evidence that it is also important to cardiovascular and kidney pathology, although the underlying mechanisms are not elucidated so far. Thus, we investigated in a mice model of diet-induced obesity and diabetes if renal histopathological changes are associated with the expression of RANKL/RANK/OPG system and matrix metalloproteinases (MMPs). Three months old C57BL/6 mice were fed with control (C) AIN93 M diet or high-fat high sucrose (HFHS) diets for 21 weeks (CEUA/UFF #647/15). The two groups presented weight gain, but it was higher in the HFHS group compared to the C group (+35%, P = 0.0001). The HFHS group also had increased epididymal, inguinal and retroperitoneal fat pad weight (+121%, P = 0.0006; +287%, P = 0.0007 and; +286%, P < 0.0001, respectively), and hyperglycemia (+43%, P = 0.02). The kidney of some HFHS fed mice displayed mononuclear inflammatory cell infiltrate (40%), perivascular fibrosis (20%), and focal tubule mineralization (20%). Glomeruli hypertrophy was not detected. Unexpectedly, OPG, RANK, MMP-2, and MMP-9 expression was not altered in HFHS groups (Western blot analysis). In conclusion, the expression of RANKL/RANK/OPG system proteins and MMPs was not influenced by diet-induced obesity and diabetes in the kidney of male C57BL/6 mice, although some adverse histopathological remodeling is noticed in the renal tissue.