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Prolonged overnutrition with fructose or fat induces metabolic derangements in rats by disrupting the crosstalk between the hypothalamus and periphery: Possible amelioration with fenofibrate.
Eur J Pharmacol. 2020 Jul 15; 879:173136.EJ

Abstract

Metabolic Syndrome (MetS) increases the risk of developing type 2 diabetes mellitus and cardiovascular complications. The crosstalk between the hypothalamus and periphery is vital for regulating food intake and energy homeostasis. However, it is impaired during MetS. The present study aimed to compare the distinct central and peripheral metabolic derangements induced by a high-fructose drink or high-fat diet, as well as the possible intervention by fenofibrate. Rats were divided into five groups: standard chow diet (SCD) group, high-fructose group (FR), high-fat group (HF), FR plus fenofibrate group (FR-F), and HF plus fenofibrate group (HF-F). FR and HF groups showed hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, steatosis, and adipocyte hypertrophy. This was associated with elevated circulating levels of proinflammatory cytokines and free fatty acids (FFAs). The latter mediators are involved in the hypothalamic inflammation and dysregulation of signaling cascades that control food intake and glucose homeostasis. The effects were more pronounced in the HF group than FR group, which were matched with the observed higher levels of plasma FFAs and cytokines. Fenofibrate administration improved not only the peripheral metabolic disturbances, but also the central disturbances associated with insulin resistance induced by FR or HF diet. This study sheds light on the pivotal role of the hypothalamus in diet-induced MetS. Furthermore, the study suggests the utmost importance of developing a standardized model of metabolic syndrome in place of the great diversity between available models, which can induce different effects and negatively impact the validity of prospective studies.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt; Pharmaceutical and Fermentation Industries Development Center (PFIDC), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab, Alexandria, 21934, Egypt.Department of Medical Biotechnology, Genetic Engineering & Biotechnology Research Institute (GEBRI), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab, Alexandria, 21934, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt. Electronic address: aamahmoud@pharmacy.zu.edu.eg.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32360834

Citation

Nabil, Mohamed, et al. "Prolonged Overnutrition With Fructose or Fat Induces Metabolic Derangements in Rats By Disrupting the Crosstalk Between the Hypothalamus and Periphery: Possible Amelioration With Fenofibrate." European Journal of Pharmacology, vol. 879, 2020, p. 173136.
Nabil M, El Demellawy MA, Mahmoud MF, et al. Prolonged overnutrition with fructose or fat induces metabolic derangements in rats by disrupting the crosstalk between the hypothalamus and periphery: Possible amelioration with fenofibrate. Eur J Pharmacol. 2020;879:173136.
Nabil, M., El Demellawy, M. A., Mahmoud, M. F., & Mahmoud, A. A. A. (2020). Prolonged overnutrition with fructose or fat induces metabolic derangements in rats by disrupting the crosstalk between the hypothalamus and periphery: Possible amelioration with fenofibrate. European Journal of Pharmacology, 879, 173136. https://doi.org/10.1016/j.ejphar.2020.173136
Nabil M, et al. Prolonged Overnutrition With Fructose or Fat Induces Metabolic Derangements in Rats By Disrupting the Crosstalk Between the Hypothalamus and Periphery: Possible Amelioration With Fenofibrate. Eur J Pharmacol. 2020 Jul 15;879:173136. PubMed PMID: 32360834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prolonged overnutrition with fructose or fat induces metabolic derangements in rats by disrupting the crosstalk between the hypothalamus and periphery: Possible amelioration with fenofibrate. AU - Nabil,Mohamed, AU - El Demellawy,Maha A, AU - Mahmoud,Mona F, AU - Mahmoud,Amr A A, Y1 - 2020/04/28/ PY - 2020/03/18/received PY - 2020/04/14/revised PY - 2020/04/20/accepted PY - 2020/5/4/pubmed PY - 2020/5/4/medline PY - 2020/5/4/entrez KW - Fructose KW - High-fat diet KW - Hypothalamus KW - Inflammation KW - Insulin/leptin resistance KW - Neuropeptides SP - 173136 EP - 173136 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 879 N2 - Metabolic Syndrome (MetS) increases the risk of developing type 2 diabetes mellitus and cardiovascular complications. The crosstalk between the hypothalamus and periphery is vital for regulating food intake and energy homeostasis. However, it is impaired during MetS. The present study aimed to compare the distinct central and peripheral metabolic derangements induced by a high-fructose drink or high-fat diet, as well as the possible intervention by fenofibrate. Rats were divided into five groups: standard chow diet (SCD) group, high-fructose group (FR), high-fat group (HF), FR plus fenofibrate group (FR-F), and HF plus fenofibrate group (HF-F). FR and HF groups showed hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, steatosis, and adipocyte hypertrophy. This was associated with elevated circulating levels of proinflammatory cytokines and free fatty acids (FFAs). The latter mediators are involved in the hypothalamic inflammation and dysregulation of signaling cascades that control food intake and glucose homeostasis. The effects were more pronounced in the HF group than FR group, which were matched with the observed higher levels of plasma FFAs and cytokines. Fenofibrate administration improved not only the peripheral metabolic disturbances, but also the central disturbances associated with insulin resistance induced by FR or HF diet. This study sheds light on the pivotal role of the hypothalamus in diet-induced MetS. Furthermore, the study suggests the utmost importance of developing a standardized model of metabolic syndrome in place of the great diversity between available models, which can induce different effects and negatively impact the validity of prospective studies. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/32360834/Prolonged_overnutrition_with_fructose_or_fat_induces_metabolic_derangements_in_rats_by_disrupting_the_crosstalk_between_the_hypothalamus_and_periphery:_Possible_amelioration_with_fenofibrate L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(20)30228-4 DB - PRIME DP - Unbound Medicine ER -
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