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Article

Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome

1
Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia
2
Food, Nutrition, and Lifestyle Research Unit, King Fahd for Medical Research Centre, King Abdulaziz University, Jeddah 21465, Saudi Arabia
3
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
4
Physiology Department, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
5
Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
6
Faculty Development Unit, Physiological Science and Medical Education Department, Fakeeh College for Medical Sciences, Jeddah 23323, Saudi Arabia
*
Author to whom correspondence should be addressed.
Brain Sci. 2023, 13(10), 1383; https://doi.org/10.3390/brainsci13101383
Submission received: 4 September 2023 / Revised: 25 September 2023 / Accepted: 27 September 2023 / Published: 28 September 2023
(This article belongs to the Section Molecular and Cellular Neuroscience)

Abstract

Brain insulin resistance is linked to metabolic syndrome (MetS). A low-carbohydrate, high-fat (LCHF) diet has been proposed to have a protective effect. Therefore, this study aimed to investigate the brain insulin resistance markers in a rat animal model of MetS and the protective effects of the LCHF diet. Four groups of male rats (10/group) were created. Group I (Control) was fed a regular diet. Groups II–IV were injected with dexamethasone (DEX) to induce MetS. Group II received DEX with a regular diet. Group III (DEX + LCHF) rates were fed a low-carbohydrate, high-fat diet, while Group IV (DEX + HCLF) rats were fed a high-carbohydrate, low-fat (HCLF) diet. At the end of the four-week experiment, HOMA-IR was calculated. Moreover, cerebral gene expression analysis of S-100B, BDNF, TNF-α, IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, Bax, Bcl-2, and caspase-3 was carried out. In the DEX group, rats showed a significant increase in the HOMA-IR and a decrease in the gene expression of IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, BDNF, and Bcl2, with a concomitant rise in S100B, TNF-α, Bax, and caspase-3. The LCHF diet group showed a significantly opposite effect on all parameters. In conclusion, MetS is associated with dysregulated cerebral gene expression of BDNF, S100B, and TNF-α and disturbed IGF-1 signaling, with increased apoptosis and neuroinflammation. Moreover, the LCHF diet showed a protective effect, as evidenced by preservation of the investigated biochemical and molecular parameters.
Keywords: metabolic syndrome; brain insulin resistance; S100B; BDNF; TNF-α; IGF-1; IGF-1R; IGFBP-2; IGFBP-5; Bax; Bcl-2; caspase-3; low carbohydrate-high fat diet metabolic syndrome; brain insulin resistance; S100B; BDNF; TNF-α; IGF-1; IGF-1R; IGFBP-2; IGFBP-5; Bax; Bcl-2; caspase-3; low carbohydrate-high fat diet

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MDPI and ACS Style

Bima, A.; Eldakhakhny, B.; Alamoudi, A.A.; Awan, Z.; Alnami, A.; Abo-Elkhair, S.M.; Sakr, H.; Ghoneim, F.M.; Elsamanoudy, A. Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome. Brain Sci. 2023, 13, 1383. https://doi.org/10.3390/brainsci13101383

AMA Style

Bima A, Eldakhakhny B, Alamoudi AA, Awan Z, Alnami A, Abo-Elkhair SM, Sakr H, Ghoneim FM, Elsamanoudy A. Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome. Brain Sciences. 2023; 13(10):1383. https://doi.org/10.3390/brainsci13101383

Chicago/Turabian Style

Bima, Abdulhadi, Basmah Eldakhakhny, Aliaa A. Alamoudi, Zuhier Awan, Abrar Alnami, Salwa Mohamed Abo-Elkhair, Hussein Sakr, Fatma Mohamed Ghoneim, and Ayman Elsamanoudy. 2023. "Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome" Brain Sciences 13, no. 10: 1383. https://doi.org/10.3390/brainsci13101383

APA Style

Bima, A., Eldakhakhny, B., Alamoudi, A. A., Awan, Z., Alnami, A., Abo-Elkhair, S. M., Sakr, H., Ghoneim, F. M., & Elsamanoudy, A. (2023). Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome. Brain Sciences, 13(10), 1383. https://doi.org/10.3390/brainsci13101383

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