Research Alert


Neuropathy, characterized by a “pins and needles” sensation and reduced touch sensitivity, is the most common complication of type 2 diabetes. It is accompanied by increased saturated fatty acids (SFAs) in blood. Replacing dietary SFAs with monounsaturated fatty acids (MOUFAs) can improve metabolism in pre-diabetic individuals, but whether it can also prevent neuropathy is unknown. This group studied mice fed either a SFA-rich high fat diet or SFA-rich then switched to a MOUFA-rich high fat diet. Both groups developed metabolic dysfunction and weight gain. However, the group that switched to a MOUFA-rich diet showed restored nerve conduction, higher nerve fiber density in limbs and protected mitochondrial function in sensory nerves. The study strongly supports the use of dietary monounsaturated fats in the treatment of neuropathy in pre-diabetic and type 2 diabetic patients.

Full abstract, to be presented at the American Neurological Association 2019 Annual Meeting (October 13-15 in St. Louis):

Saturated and Monounsaturated Fatty Acids Differentially Regulate Nerve Function in Murine Models of Obesity

Amy E. Rumora, Ph.D., Giovanni LoGrasso, B.S., John M. Hayes, B.S., Faye E. Mendelson, B.S., Maegan A. Tabbey, B.S., Julia A. Haidar, B.S., Stephen I. Lentz, Ph.D., Eva L. Feldman, M.D., Ph.D.. University of Michigan, Ann Arbor, MI, USA.

Neuropathy is the most prevalent complication of type 2 diabetes (T2D) and prediabetes. The progression of neuropathy in prediabetic and T2D patients correlates with dyslipidemia characterized by elevated levels of circulating saturated fatty acids (SFAs). Recent studies indicate that dietary replacement of SFAs with monounsaturated fatty acids (MUFAs) improves the metabolic health of prediabetic and T2D patients; however, the differential effect of dietary SFAs and MUFAs on neuropathy is unknown. This study examined the impact of SFAs and MUFAs on nerve function. Three groups of mice were fed diets with varying fatty acid composition from 6 to 24 weeks including a standard diet (SD), a SFA-rich high fat diet (HFD); and a SFA-rich HFD until 16 weeks followed by a MUFA-rich HFD (HFD-MUFA) until 24 weeks. At 24 weeks, both HFD and HFD-MUFA groups exhibited impaired glucose tolerance, increased body weight, and higher body fat mass compared to the SD group. Despite equivalent metabolic dysfunction in HFD and HFD-MUFA groups, the HFD-MUFA mice exhibited a complete restoration in sural and sciatic nerve conduction velocity. In parallel, nerve fiber density was significantly increased in HFD-MUFA mice compared to HFD mice. To identify molecular changes underlying the restoration of sensory function in HFD-MUFA mice, we next evaluated the effect of SFA palmitate and MUFA oleate on mitochondrial dynamics in cultured dorsal root ganglion (DRG) sensory neurons. Diabetic concentrations of palmitate impaired mitochondrial transport and function in DRG axons. Supplementation of palmitate treatments with oleate prevented impairment of axonal mitochondrial transport and restored mitochondrial membrane potential and ATP production in DRG neurons. In addition, oleate promoted the formation of intracellular lipid droplets in DRG axons suggesting that lipid droplets may sequester palmitate to prevent palmitate-induced mitochondrial dysfunction. Together, these data support the contention that the development of neuropathy is related to mitochondrial dysfunction induced by SFAs, and that lipid droplet formation may underlie the beneficial effects of MUFAs on mitochondrial dynamics and neuronal function. Importantly, SFA-induced nerve damage and mitochondrial dysfunction is reversed by MUFAs emphasizing the potential for MUFAs as a treatment for neuropathy in prediabetic and T2D patients.

All abstracts from ANA2019 will be available under embargo starting October 4. Contact Katherine Pflaumer ([email protected]) for full meeting abstracts, and for call-in information for the ANA2019 Media Roundtable (Oct. 15, 11 a.m. US Central).

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American Neurological Association Annual Meeting, October 13-15, 2019