Abstract
Emerging evidence suggests that dyslipidemia is an independent risk factor for diabetic neuropathy (DN) (reviewed by Vincent et al. 2009). To experimentally determine how dyslipidemia alters DN, we quantified neuropathic symptoms in diabetic mice fed a high-fat diet. Streptozotocin-induced diabetic C57BL/6 mice fed a high-fat diet developed dyslipidemia and a painful neuropathy (mechanical allodynia) instead of the insensate neuropathy (mechanical insensitivity) that normally develops in this strain. Nondiabetic mice fed a high-fat diet also developed dyslipidemia and mechanical allodynia. Thermal sensitivity was significantly reduced in diabetic compared to nondiabetic mice, but was not worsened by the high-fat diet. Moreover, diabetic mice fed a high-fat diet had significantly slower sensory and motor nerve conduction velocities compared to nondiabetic mice. Overall, dyslipidemia resulting from a high-fat diet may modify DN phenotypes and/or increase risk for developing DN. These results provide new insight as to how dyslipidemia may alter the development and phenotype of diabetic neuropathy.
Highlights
Diabetic neuropathy (DN) is a principal chronic complication of both type 1 and type 2 diabetes and affects over half of diabetic patients [1,2,3]
Diabetic mice on the standard diet consumed at least 2 times as many kcals/day compared to all other groups (DbStd 29.7 ± 1.8 kcals/day; DbHF 15.2 ± 7.8 kcals/day, P < 0.05 for diabetic standard diet (DbStd) versus nondiabetic standard diet (NdStd), nondiabetic high-fat diet (NdHF), and DbHF)
Future studies will investigate the role of spinal inflammation in high-fat diet-induced mechanical allodynia. These results demonstrate that a high-fat diet fed to STZ-induced diabetic C57BL/6 mice significantly alters the phenotype of neural symptoms by inducing a painful neuropathy instead of the insensate neuropathy that we have previously observed in this inbred strain
Summary
Diabetic neuropathy (DN) is a principal chronic complication of both type 1 and type 2 diabetes and affects over half of diabetic patients [1,2,3]. A dying back-type distal axon degeneration is the common underlying feature associated with DN [8]. It is thought that nerve dysfunction and degeneration leads to sensorimotor deficits, reduced nerve conduction velocities, and decreased epidermal innervation, all of which are characteristic signs of DN in human patients and animal models [7, 9]. It is clear that hyperglycemia plays a key role in the development and progression of DN [4, 9,10,11,12], a combination of multiple etiologies is likely responsible for axonal degeneration leading to the various types of neuropathy in diabetic patients [4, 10, 11]. Despite extensive study of proposed mechanisms, it remains unclear why some patients develop insensate versus painful symptoms and how underlying pathological mechanisms determine DN progression and phenotype
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