Niraula Anzela, Hansen Kim, Bullock Kristin M, Erickson Michelle A, Banks William A
Neuroscience Program, Department of Psychological and Brain Sciences, Colgate University, Hamilton, NY 13346, USA.
Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Endocrinology. 2025 Jun 10;166(8). doi: 10.1210/endocr/bqaf095.
High-fat diet (HFD) consumption increases the risk of metabolic syndrome as manifested by insulin resistance, fatty liver, hypertriglyceridemia, and diabetes mellitus type 2. Blood-brain barrier (BBB) disruptions and impaired BBB transport of metabolic hormones, including leptin, insulin, and ghrelin, occur in diabetes mellitus type 2 and contribute to metabolic dysregulation and cognitive impairment. However, it is unclear whether the BBB changes are caused by the HFD, obesity, insulin resistance, elevated glucose or triglyceride levels, or other aspects of the metabolic syndrome. This study examined the effects of chronic HFD and an early stage of metabolic syndrome on BBB disruption and transport of insulin, leptin, and ghrelin. Mice on the HFD demonstrated obesity, increases in insulin, leptin, plasminogen activator inhibitor-1, and resistin, fatty liver and hyperglycerolemia, without elevations in glucose, triglycerides, ghrelin, glucagon, gastric inhibitory polypeptide, or glucagon-like peptide. The vascular markers of sucrose and albumin did not show BBB disruption. HFD did not alter the rate of insulin, leptin, or ghrelin transport across the BBB. However, leptin binding to the luminal surface of the BBB was greater in the hypothalamus and reduced for the rest of the brain with HFD treatment. The liver uptake of insulin, leptin, and ghrelin was reduced in the HFD group. Overall, our findings indicate that chronic HFD consumption with concomitant obesity and insulin resistance in the absence of hyperglycemia does not result in BBB disruption or altered BBB permeability to key metabolic hormones but may selectively affect vascular binding of important metabolic hormones in the brain and liver.
食用高脂饮食（HFD）会增加代谢综合征的风险，表现为胰岛素抵抗、脂肪肝、高甘油三酯血症和2型糖尿病。2型糖尿病会出现血脑屏障（BBB）破坏以及代谢激素（包括瘦素、胰岛素和胃饥饿素）的血脑屏障转运受损，进而导致代谢失调和认知障碍。然而，尚不清楚血脑屏障的变化是由高脂饮食、肥胖、胰岛素抵抗、血糖或甘油三酯水平升高，还是代谢综合征的其他方面引起的。本研究考察了慢性高脂饮食和代谢综合征早期阶段对血脑屏障破坏以及胰岛素、瘦素和胃饥饿素转运的影响。高脂饮食喂养的小鼠出现了肥胖、胰岛素、瘦素、纤溶酶原激活物抑制剂-1和抵抗素增加、脂肪肝和高甘油三酯血症，但血糖、甘油三酯、胃饥饿素、胰高血糖素、胃抑肽或胰高血糖素样肽并未升高。蔗糖和白蛋白的血管标志物未显示血脑屏障破坏。高脂饮食并未改变胰岛素、瘦素或胃饥饿素穿过血脑屏障的转运速率。然而，高脂饮食处理后，下丘脑血脑屏障管腔表面的瘦素结合增加，而大脑其他部位则减少。高脂饮食组肝脏对胰岛素、瘦素和胃饥饿素的摄取减少。总体而言，我们的研究结果表明，在无高血糖的情况下，长期食用高脂饮食并伴有肥胖和胰岛素抵抗，不会导致血脑屏障破坏或血脑屏障对关键代谢激素的通透性改变，但可能会选择性地影响大脑和肝脏中重要代谢激素的血管结合。
