Effect of Dietary Content of Menhaden Oil with or without Salsalate on Neuropathic Endpoints in High-Fat-Fed/Low-Dose Streptozotocin-Treated Sprague Dawley Rats

Davidson, Eric P.; Coppey, Lawrence J.; Shevalye, Hanna; Obrosov, Alexander; Yorek, Mark A.

doi:10.1155/2018/2967127

Cited by 15 publications

(17 citation statements)

References 37 publications

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“…Furthermore, this lack of pretreatment tests makes it difficult to completely determine if treatment slowed progression or reversed the nerve damages observed. Because slowing of MNCV was not observed in this study, there might be a difference in the neuropathic phenotype between the animals of the present study and the animals used in other studies [10,11,16]. This is further supported by the different effects of long-term diabetes on thermal induced pain (hypoalgesia vs. hyperalgesia) between the present study (Figures 4(a) and 4(b)) and other studies [10,11,16].…”

supporting

confidence: 60%

“…In this study, diabetes did not cause large nerve fiber damage when assessed by MNCV (Figure 4(d)). That 16 weeks of untreated diabetes was not enough to cause a decline in MNCV was surprising because decreased MNCV has been observed in other studies of similar length using similar rat models of T2D [10,11,16]. Increased sorbitol and decreased myo-inositol content in the sciatic nerve have The response variables (a) thermal induced pain and (b) intraepidermal nerve fiber density (IENFD) were evaluated in an analysis of covariance using stepwise backwards reduction leaving only significant covariates with group as class variable and HbA 1c %, sciatic nerve sorbitol content, triglyceride (TG), and total cholesterol (TC) as covariates to investigate the influence of the covariates on nerve damage.…”

Section: Discussionmentioning

confidence: 88%

“…Because slowing of MNCV was not observed in this study, there might be a difference in the neuropathic phenotype between the animals of the present study and the animals used in other studies [10,11,16]. This is further supported by the different effects of long-term diabetes on thermal induced pain (hypoalgesia vs. hyperalgesia) between the present study (Figures 4(a) and 4(b)) and other studies [10,11,16]. Vendor-derived differences in rats are a described phenomenon in other studies in respect to different behavioral, metabolic, and pain-related parameters [45][46][47] and might explain the different observations.…”

mentioning

confidence: 75%

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Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes

ANDREASEN

Kirk

Fledelius

et al. 2020

Journal of Diabetes Research

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Introduction. Current clinical guidelines for management of diabetic peripheral neuropathy (DPN) emphasize good glycemic control. However, this has limited effect on prevention of DPN in type 2 diabetic (T2D) patients. This study investigates the effect of insulin treatment on development of DPN in a rat model of T2D to assess the underlying causes leading to DPN. Methods. Twelve-week-old male Sprague-Dawley rats were allocated to a normal chow diet or a 45% kcal high-fat diet. After eight weeks, the high-fat fed animals received a mild dose of streptozotocin to induce hyperglycemia. Four weeks after diabetes induction, the diabetic animals were allocated into three treatment groups receiving either no insulin or insulin-releasing implants in a high or low dose. During the 12-week treatment period, blood glucose and body weight were monitored weekly, whereas Hargreaves’ test was performed four, eight, and 12 weeks after treatment initiation. At study termination, several blood parameters, body composition, and neuropathy endpoints were assessed. Results. Insulin treatment lowered blood glucose in a dose-dependent manner. In addition, both doses of insulin lowered lipids and increased body fat percentage. High-dose insulin treatment attenuated small nerve fiber damage assessed by Hargreaves’ test and intraepidermal nerve fiber density compared to untreated diabetes and low-dose insulin; however, neuropathy was not completely prevented by tight glycemic control. Linear regression analysis revealed that glycemic status, circulating lipids, and sciatic nerve sorbitol level were all negatively associated with the small nerve fiber damage observed. Conclusion. In summary, our data suggest that high-dose insulin treatment attenuates small nerve fiber damage. Furthermore, data also indicate that both poor glycemic control and dyslipidemia are associated with disease progression. Consequently, this rat model of T2D seems to fit well with progression of DPN in humans and could be a relevant preclinical model to use in relation to research investigating treatment opportunities for DPN.

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confidence: 60%

Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 75%

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Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes

ANDREASEN

Kirk

Fledelius

et al. 2020

Journal of Diabetes Research

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“…This reversal of neuropathy progression suggests that fatty acid saturation, not prediabetes, is the main factor underlying neuropathy progression in HFD-fed obese mice. Partial restoration of nerve function is also seen in diabetic rodent models fed a HFD supplemented with Menhaden oil containing mixtures of PUFAs (Shevalye et al, 2015;Yorek et al, 2017;Coppey et al, 2018;Davidson et al, 2018). However, supplementation with MUFA-rich olive oil did not restore nerve function in obese rats (Coppey et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The Divergent Roles of Dietary Saturated and Monounsaturated Fatty Acids on Nerve Function in Murine Models of Obesity

Rumora¹,

Lograsso²,

Hayes³

et al. 2019

J. Neurosci.

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Neuropathy is the most common complication of prediabetes and diabetes and presents as distal-to-proximal loss of peripheral nerve function in the lower extremities. Neuropathy progression and disease severity in prediabetes and diabetes correlates with dyslipidemia in man and murine models of disease. Dyslipidemia is characterized by elevated levels of circulating saturated fatty acids (SFAs) that associate with the progression of neuropathy. Increased intake of monounsaturated fatty acid (MUFA)-rich diets confers metabolic health benefits; however, the impact of fatty acid saturation in neuropathy is unknown. This study examines the differential effect of SFAs and MUFAs on the development of neuropathy and the molecular mechanisms underlying the progression of the complication. Male mice Mus musculus fed a high-fat diet rich in SFAs developed robust peripheral neuropathy. This neuropathy was completely reversed by switching the mice from the SFA-rich high-fat diet to a MUFA-rich high-fat diet; nerve conduction velocities and intraepidermal nerve fiber density were restored. A MUFA oleate also prevented the impairment of mitochondrial transport and protected mitochondrial membrane potential in cultured sensory neurons treated with mixtures of oleate and the SFA palmitate. Moreover, oleate also preserved intracellular ATP levels, prevented apoptosis induced by palmitate treatment, and promoted lipid droplet formation in sensory neurons, suggesting that lipid droplets protect sensory neurons from lipotoxicity. Together, these results suggest that MUFAs reverse the progression of neuropathy by protecting mitochondrial function and transport through the formation of intracellular lipid droplets in sensory neurons.

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“…We also detected increased levels of TG acyl chains derived from the monounsaturated FA oleate in SCNs of HFD mice. Experimental and clinical studies reported beneficial effects of unsaturated FAs on nerve function (Coppey et al, 2018;Davidson et al, 2018;Shevalye et al, 2015;Yorek et al, 2017). The differential impact of oleate may be related to the lower ratio of dietary monounsaturated FAs to SFAs in the lard-based HFD chow (Coppey et al, 2018;Listenberger et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Integrated lipidomic and transcriptomic analyses identify altered nerve triglycerides in mouse models of prediabetes and type 2 diabetes

O’Brien

Guo

Eid

et al. 2020

Disease Models &Amp; Mechanisms

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Peripheral neuropathy (PN) is a complication of prediabetes and type 2 diabetes (T2D). Increasing evidence suggests that factors besides hyperglycaemia contribute to PN development, including dyslipidaemia. The objective of this study was to determine differential lipid classes and altered gene expression profiles in prediabetes and T2D mouse models in order to identify the dysregulated pathways in PN. Here, we used high-fat diet (HFD)-induced prediabetes and HFD/streptozotocin (STZ)-induced T2D mouse models that develop PN. These models were compared to HFD and HFD-STZ mice that were subjected to dietary reversal. Both untargeted and targeted lipidomic profiling, and gene expression profiling were performed on sciatic nerves. Lipidomic and transcriptomic profiles were then integrated using complex correlation analyses, and biological meaning was inferred from known lipid-gene interactions in the literature. We found an increase in triglycerides (TGs) containing saturated fatty acids. In parallel, transcriptomic analysis confirmed the dysregulation of lipid pathways. Integration of lipidomic and transcriptomic analyses identified an increase in diacylglycerol acyltransferase 2 (DGAT2), the enzyme required for the last and committed step in TG synthesis. Increased DGAT2 expression was present not only in the murine models but also in sural nerve biopsies from hyperlipidaemic diabetic patients with PN. Collectively, these findings support the hypothesis that abnormal nerve-lipid signalling is an important factor in peripheral nerve dysfunction in both prediabetes and T2D.

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Effect of Dietary Content of Menhaden Oil with or without Salsalate on Neuropathic Endpoints in High-Fat-Fed/Low-Dose Streptozotocin-Treated Sprague Dawley Rats

Cited by 15 publications

References 37 publications

Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes

Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes

The Divergent Roles of Dietary Saturated and Monounsaturated Fatty Acids on Nerve Function in Murine Models of Obesity

Integrated lipidomic and transcriptomic analyses identify altered nerve triglycerides in mouse models of prediabetes and type 2 diabetes

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