{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:19:01Z","timestamp":1791137941330,"version":"4.1.0"},"reference-count":59,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:p>Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of I\u03baB\u03b1 in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.<\/jats:p>","DOI":"10.1152\/ajpregu.00449.2010","type":"journal-article","created":{"date-parts":[[2010,8,12]],"date-time":"2010-08-12T03:15:21Z","timestamp":1281582921000},"page":"R1082-R1090","source":"Crossref","is-referenced-by-count":139,"title":["Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet"],"prefix":"10.1152","volume":"299","author":[{"given":"Jill K.","family":"Morris","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory L.","family":"Bomhoff","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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