title: Effects of discontinuing a high-fat diet on mitochondrial proteins and 6-hydroxydopamine-induced dopamine depletion in rats.
abstract: Diet-induced obesity can increase the risk for developing age-related neurodegenerative diseases including Parkinson's disease (PD). Increasing evidence suggests that mitochondrial and proteasomal mechanisms are involved in both insulin resistance and PD. The goal of this study was to determine whether diet intervention could influence mitochondrial or proteasomal protein expression and vulnerability to 6-Hydroxydopamine (6-OHDA)-induced nigrostriatal dopamine (DA) depletion in rats' nigrostriatal system. After a 3 month high-fat diet regimen, we switched one group of rats to a low-fat diet for 3 months (HF-LF group), while the other half continued with the high-fat diet (HF group). A chow group was included as a control. Three weeks after unilateral 6-OHDA lesions, HF rats had higher fasting insulin levels and higher Homeostasis model assessment of insulin resistance (HOMA-IR), indicating insulin resistance. HOMA-IR was significantly lower in HF-LF rats than HF rats, indicating that insulin resistance was reversed by switching to a low-fat diet. Compared to the Chow group, the HF group exhibited significantly greater DA depletion in the substantia nigra but not in the striatum. DA depletion did not differ between the HF-LF and HF group. Proteins related to mitochondrial function (such as AMPK, PGC-1α), and to proteasomal function (such as TCF11/Nrf1) were influenced by diet intervention, or by 6-OHDA lesion. Our findings suggest that switching to a low-fat diet reverses the effects of a high-fat diet on systemic insulin resistance, and mitochondrial and proteasomal function in the striatum. Conversely, they suggest that the effects of the high-fat diet on nigrostriatal vulnerability to 6-OHDA-induced DA depletion persist.
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors: Delin
authors: D
authors: Ma
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Jeffrey M
authors: JM
authors: Shuler
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Kayla D
authors: KD
authors: Raider
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Robert S
authors: RS
authors: Rogers
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Joshua L
authors: JL
authors: Wheatley
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Paige C
authors: PC
authors: Geiger
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: JSTANFORD@kumc.edu.
authors: John A
authors: JA
authors: Stanford
mesh_terms: D000818:Animals; D001835:Body Weight; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects*; D004298:Dopamine / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000178:diet therapy / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D016627:Oxidopamine; D005947:Glucose; D004298:Dopamine
keywords: 6-Hydroxydopamine; Dopamine; Obesity