Phenotypic Changes in Diabetic Neuropathy Induced by a High-Fat Diet in Diabetic C57Bl/6 Mice

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.

Effect of one month duration ketogenic and non-ketogenic high fat diets on mouse brain bioenergetic infrastructure

“…In any case, at the end of the fast glucose levels were lower in the ketogenic diet-treated mice at a time when insulin levels were comparable between groups. The HOMA-IR calculation, therefore, suggests the ketogenic diet enhanced peripheral insulin sensitivity, at least when compared to the Western high fat diet, which over an adequate duration would itself predictably induce peripheral insulin resistance in C57Bl/6J mice (Surwit et al 1988, Sandu et al 2005, Guilford et al 2011). …”

Diabetic Peripheral Neuropathy: Should a Chaperone Accompany Our Therapeutic Approach?

“…Remarkably, a recent report indicates that superimposing dyslipidemia on a diabetic background can differentially affect sensory modalities associated with DPN. Diabetic C57BL/6 mice given a standard chow exhibited a mechanical hypoalgesia (an insensate neuropathy), whereas diabetic mice placed on a high-fat diet exhibited a mechanical allodynia (a painful neuropathy) (Guilford et al, 2011). On the other hand, the high-fat diet did not significantly worsen the thermal hypoalgesia that was manifested in the diabetic mice.…”

Macrophage-mediated glucolipotoxicity via myeloid-related protein 8/toll-like receptor 4 signaling in diabetic nephropathy

“…In STZ + HFD mice, there are several reports describing vascular complications such as cardiovascular dysfunction [21], retinopathy [22], neuropathy [23] and nephropathy [5, 24]. …”