Abstract
BackgroundThe rising epidemic of obesity is associated with cognitive decline and is considered as one of the major risk factors for neurodegenerative diseases. Neuroinflammation is a critical component in the progression of several neurological and neurodegenerative diseases. Increased metabolic flux to the brain during overnutrition and obesity can orchestrate stress response, blood-brain barrier (BBB) disruption, recruitment of inflammatory immune cells from peripheral blood and microglial cells activation leading to neuroinflammation. The lack of an effective treatment for obesity-associated brain dysfunction may have far-reaching public health ramifications, urgently necessitating the identification of appropriate preventive and therapeutic strategies. The objective of our study was to investigate the neuroprotective effects of Momordica charantia (bitter melon) on high-fat diet (HFD)-associated BBB disruption, stress and neuroinflammatory cytokines.MethodsC57BL/6 female mice were fed HFD with and without bitter melon (BM) for 16 weeks. BBB disruption was analyzed using Evans blue dye. Phosphate-buffered saline (PBS) perfused brains were analyzed for neuroinflammatory markers such as interleukin-22 (IL-22), IL-17R, IL-16, NF-κB1, and glial cells activation markers such as Iba1, CD11b, GFAP and S100β. Additionally, antioxidant enzymes, ER-stress proteins, and stress-resistant transcription factors, sirtuin 1 (Sirt1) and forkhead box class O transcription factor (FoxO) were analyzed using microarray, quantitative real-time RT-PCR, western immunoblotting and enzymatic assays. Systemic inflammation was analyzed using cytokine antibody array.ResultsBM ameliorated HFD-associated changes in BBB permeability as evident by reduced leakage of Evans blue dye. HFD-induced glial cells activation and expression of neuroinflammatory markers such as NF-κB1, IL-16, IL-22 as well as IL-17R were normalized in the brains of mice supplemented with BM. Similarly, HFD-induced brain oxidative stress was significantly reduced by BM supplementation with a concomitant reduction in FoxO, normalization of Sirt1 protein expression and up-regulation of Sirt3 mRNA expression. Furthermore, plasma antioxidant enzymes and pro-inflammatory cytokines were also normalized in mice fed HFD with BM as compared to HFD-fed mice.ConclusionsFunctional foods such as BM offer a unique therapeutic strategy to improve obesity-associated peripheral inflammation and neuroinflammation.
Highlights
The rising epidemic of obesity is associated with cognitive decline and is considered as one of the major risk factors for neurodegenerative diseases
Our study investigates the neuroprotective effects of Momordica charantia, a staple of traditional Okinawan diet, to ameliorate obesity-associated neuroinflammation and stress
The mixture was filtered to remove the particulates, and bitter melon (BM) modulates metabolic parameters We have previously demonstrated that BM has no significant effect on food or water intake, reduced overall weight gain by 21% as compared to mice fed high-fat diet (HFD) with a concomitant reduction in hepatic and plasma lipids and improvement in glucose tolerance [19]
Summary
The rising epidemic of obesity is associated with cognitive decline and is considered as one of the major risk factors for neurodegenerative diseases. The objective of our study was to investigate the neuroprotective effects of Momordica charantia (bitter melon) on high-fat diet (HFD)associated BBB disruption, stress and neuroinflammatory cytokines. The rising epidemic of obesity is associated with diabetes and cardiovascular diseases, and brain dysfunction and early onset of dementia [1]. High-fat diet (HFD) induces pro-inflammatory cytokines including tumor necrosis factor a (TNFa), interleukin (IL-1b) and IL6 in peripheral tissues as well as hypothalamus, raising the possibility of a cross-talk between peripheral and neuroinflammation [2,3]. Therapeutic and preventive strategies to reduce obesity require multiple therapies and life-style changes that may not necessarily ameliorate neuronal insults. Okinawan centenarians demonstrate normal cognitive function such as attention span and memory, and delayed onset of dementia, which was associated with various life-style factors including consumption of bitter functional foods [14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
