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Mechanistic correlation of molecular pathways in obesity-mediated stroke pathogenesis

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Abstract

Obesity, a prominent risk factor for the development of heart attacks and several cardiovascular ailments. Obesity ranks as the second most significant avoidable contributor to mortality, whereas stroke stands as the second leading cause of death on a global scale. While changes in lifestyle have been demonstrated to have significant impacts on weight management, the long-term weight loss remains challenging, and the global prevalence of obesity continues to rise. The pathophysiology of obesity has been extensively studied during the last few decades, and an increasing number of signal transduction pathways have been linked to obesity preclinically. This review is focused on signaling pathways, and their respective functions in regulating the consumption of fatty food as well as accumulation of adipose tissue, and the resulting morphological and cognitive changes in the brain of individuals with obesity. We have also emphasized the recent progress in the mechanisms behind the emergence of obesity, as elucidated by both experimental and clinical investigations. The mounting understanding of signaling transduction may shed light on the future course of obesity research as we move into a new era of precision medicine.

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Abbreviations

ATMs:

Adipose tissue macrophages

BAT:

Brown adipose tissue

BBB:

Blood-brain barrier

BMI:

Body mass index

CCL2:

C-C motif chemokine 2

CXCL1:

C-X-C motif chemokine 1

HPA:

Hypothalamic-pituitary-adrenal

IL:

1-Cytokines interleukin-1

IL:

6-Interleukin-6

LDL:

Low-density lipoprotein

MCP:

1-Monocyte chemoattractant protein 1

MELT:

Middle cerebral artery embolism local fibrinolytic intervention

RCTs:

Randomized clinical trials

TGs:

Triacylglycerols

TNF:

α-Tumor necrosis factor

UCP:

1-Uncoupled protein

WAT:

White adipose tissue

WHR:

Waist-to-hip ratio

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Acknowledgements

The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India for providing the necessary facilities to carry out the research work.

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  1. Chitkara College of Pharmacy, Chitkara University, Punjab, 140401, India

    Heena Khan, Chanchal Tiwari, Palak Kalra, Daksha Vyas, Amarjot Kaur Grewal & Thakur Gurjeet Singh

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  1. Heena Khan
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  2. Chanchal Tiwari
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Heena Khan was involved in writing––original draft preparation and revising; Thakur Gurjeet Singh supervision; Chanchal Tiwari, Palak Kalra and Daksha Vyas were involved in writing––original draft preparation; Amarjot Kaur Grewal, Thakur Gurjeet Singh performed reviewing and editing. All authors read and approved the final manuscript.

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Khan, H., Tiwari, C., Kalra, P. et al. Mechanistic correlation of molecular pathways in obesity-mediated stroke pathogenesis. Pharmacol. Rep 76, 463–474 (2024). https://doi.org/10.1007/s43440-024-00590-9

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