Fig. 6: The effects of hypothalamic PDK2 overexpression on diabetes-induced inflammatory cytokines, food intake, blood glucose, and the expression of hypothalamic neuropeptides in Pdk2 KO mice. | Nature Communications

Fig. 6: The effects of hypothalamic PDK2 overexpression on diabetes-induced inflammatory cytokines, food intake, blood glucose, and the expression of hypothalamic neuropeptides in Pdk2 KO mice.

From: Astrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes

Fig. 6: The effects of hypothalamic PDK2 overexpression on diabetes-induced inflammatory cytokines, food intake, blood glucose, and the expression of hypothalamic neuropeptides in Pdk2 KO mice.The alternative text for this image may have been generated using AI.

To further determine the role of hypothalamic PDK2 in diabetes-induced neuroinflammation and dysregulation of feeding behavior, we administered Ad-PDK2-GFP or Ad-GFP (1.0 × 109 pfu) via the icv route 1 w before STZ injection. The schematic diagram shows the experimentation timeline and the route of administration (a). PDK2 protein levels (###p = 4.5E-5, KO + Ad-PDK2-GFP + STZ) in the hypothalamus after 3 w of STZ and 4 w of adenovirus injection were assessed by Western blot analysis (b). Western blot band quantification for PDK2 protein levels normalized to α-tubulin. The relative expression of Tnf-α (##p = 0.0030, KO + Ad-PDK2-GFP + STZ), Il-1β (#p = 0.0380, KO + Ad-PDK2-GFP + STZ), and Il-6 (##p = 0.0020, KO + Ad-PDK2-GFP + STZ) mRNA in the hypothalamic tissues isolated from Ad-PDK2-GFP or Ad-GFP and WT mice was evaluated by real-time RT-PCR (c). Food intake (*p = 0.0130, KO + Ad-PDK2-GFP + STZ at 28 d) (d) and fasting blood glucose levels (*p = 0.0127, KO + Ad-PDK2-GFP + STZ at 28 d) (e) were assessed following Ad-PDK2-GFP or Ad-GFP and STZ administration. Arrows indicate the time points of adenovirus (Ad) and STZ administration. The relative expression of Npy (#p = 0.0489, KO + Ad-PDK2-GFP + STZ), Agrp (##p = 0.0090, KO + Ad-PDK2-GFP + STZ), and Pomc (#p = 0.0270, KO + Ad-PDK2-GFP + STZ) mRNA in the hypothalamic tissues isolated from Ad-PDK2-GFP or Ad-GFP and STZ-injected mice just after completion of behavioral assessments was evaluated by real-time RT-PCR (f). Results for mRNA expression are displayed as the fold increase of mRNA expression normalized to Gapdh. *p < 0.05, **p < 0.01, or ***p < 0.001 versus the vehicle-treated control animals (b, c, f) or STZ/Ad-GFP + STZ-treated animals (d, e); #p < 0.05, ##p < 0.01 between the indicated groups. One-way ANOVA (b, c, f) and two-way ANOVA with Tukey’s post hoc test (d, e), n = 3 (b), n = 4 (c, f), and n = 6 (d, e); mean ± SEM. Value of “n” indicates the number of animals. Source data are provided as a Source data file. d day(s); STZ streptozotocin; pfu plaque-forming unit; ns not significant; ND not detected.

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