Experimental dopaminergic neuron lesion at the area of the biological clock pacemaker, suprachiasmatic nuclei (SCN) induces metabolic syndrome in rats

Abstract Background The daily peak in dopaminergic neuronal activity at the area of biological clock (hypothalamic suprachiasmatic nuclei [SCN]) is diminished obese/insulin resistant vs lean/insulin sensitive animals. impact targeted lesioning dopamine (DA) neurons specifically surrounding (and that communicate with) SCN (but not within itself) upon glucose metabolism, adipose and liver lipid gene expression, cardiovascular biology normal laboratory animals has been investigated was focus this study. Methods Female Sprague–Dawley rats received either DA neuron neurotoxic lesion by bilateral intra-cannula injection 6-hydroxydopamine (2–4 μg/side) or vehicle treatment 20 min post protriptyline ip (20 mg/kg) to protect against damage noradrenergic serotonergic neurons. Results At 16 weeks post-lesion relative treatment, peri-SCN increased weight gain (34.8%, P < 0.005), parametrial retroperitoneal fat (45% 90% respectively, 0.05), fasting plasma insulin, leptin norepinephrine levels (180%, 71%, 40% tolerance test under curve (AUC) insulin (112.5%, resistance (44%—Matsuda Index, 0.05) without altering food consumption during period. Such also induced expression several synthesis genes lipolytic gene, hormone lipase (P 0.05 for all). Liver monocyte chemoattractant protein 1 (a proinflammatory associated with metabolic syndrome) significantly elevated lesioned rats. Peri-SCN were hypertensive (systolic BP rose from 157 ± 5 175 mmHg, 0.01; diastolic 109 4 120 3 heart rate increase 368 12 406 BPM, had (40% increased, controls. Conclusions These findings indicate reduced communicating contributes sympathetic tone development syndrome, effect on feeding.