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The Divergent Roles of Dietary Saturated and Monounsaturated Fatty Acids on
Nerve Function in Murine Models of Obesity.
Authors Rumora AE, LoGrasso G, Hayes JM, Mendelson FE, Tabbey MA, Haidar JA, Lentz SI,
Feldman EL
Submitted By Submitted Externally on 5/21/2019
Status Published
Journal The Journal of neuroscience : the official journal of the Society for Neuroscience
Year 2019
Date Published 5/1/2019
Volume : Pages 39 : 3770 - 3781
PubMed Reference 30886017
Abstract 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.SIGNIFICANCE STATEMENT There is a global
epidemic of prediabetes and diabetes, disorders that represent a continuum of
metabolic disturbances in lipid and glucose metabolism. In the United States, 80
million individuals have prediabetes and 30 million have diabetes. Neuropathy is
the most common complication of both disorders, carries a high morbidity, and,
despite its prevalence, has no treatments. We report that dietary intervention
with monounsaturated fatty acids reverses the progression of neuropathy and
restores nerve function in high-fat diet-fed murine models of peripheral
neuropathy. Furthermore, the addition of the monounsaturated fatty acid oleate
to sensory neurons cultured under diabetic conditions shows that oleate prevents
impairment of mitochondrial transport and mitochondrial dysfunction through a
mechanism involving formation of axonal lipid droplets.


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