TY - JOUR
T1 - Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome
AU - Bima, Abdulhadi
AU - Eldakhakhny, Basmah
AU - Alamoudi, Aliaa A.
AU - Awan, Zuhier
AU - Alnami, Abrar
AU - Abo-Elkhair, Salwa Mohamed
AU - Sakr, Hussein
AU - Ghoneim, Fatma Mohamed
AU - Elsamanoudy, Ayman
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/9/28
Y1 - 2023/9/28
N2 - 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.
AB - 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.
KW - BDNF
KW - Bax
KW - Bcl-2
KW - IGF-1
KW - IGF-1R
KW - IGFBP-2
KW - IGFBP-5
KW - S100B
KW - TNF-α
KW - brain insulin resistance
KW - caspase-3
KW - low carbohydrate-high fat diet
KW - metabolic syndrome
UR - http://www.scopus.com/inward/record.url?scp=85175301809&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85175301809&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/22796bc3-f85c-3236-910c-c9f7ff130da9/
U2 - 10.3390/brainsci13101383
DO - 10.3390/brainsci13101383
M3 - Article
C2 - 37891752
AN - SCOPUS:85175301809
SN - 2076-3425
VL - 13
JO - Brain Sciences
JF - Brain Sciences
IS - 10
M1 - 1383
ER -