Analysis of the Effect of the TRPC4/TRPC5 Blocker, ML204, in Sucrose-Induced Metabolic Imbalance

Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast...

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Published in:	Pharmaceuticals (Basel, Switzerland) Vol. 16; no. 8; p. 1100
Main Authors:	Araújo, Mizael C, Soczek, Suzany H. S, Pontes, Jaqueline P, Pinto, Bruno A. S, França, Lucas M, Soley, Bruna da Silva, Santos, Gabriela S, Saminez, Warlison F. de Silva, Fernandes, Fernanda K. M, Lima, João L. do Carmo, Maria-Ferreira, Daniele, Rodrigues, João F. S, Quintão, Nara L. M, Monteiro-Neto, Valério, Paes, Antônio M. A, Fernandes, Elizabeth S
Format:	Journal Article
Language:	English
Published:	Basel MDPI AG 01-08-2023 MDPI
Subjects:	Adipocytes Body fat Body mass index Care and treatment Chronic illnesses Diabetes Diet fat deposition Glucose Health aspects hepatic steatosis high sucrose intake Hyperglycemia Inflammation Investigations Liver diseases Membrane proteins metabolic changes Metabolic diseases Metabolism Obesity Risk factors Sucrose TRPC4 and TRPC5 channels Vascular endothelial growth factor Weight control Brazil
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Summary:	Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast, restaurant, and processed foods. Herein, we investigated the effects of a TRPC4/TRPC5 blocker, ML204, in the metabolic imbalances triggered by early exposure to sucrose-enriched diet in mice. TRPC4 and TRPC5 belong to the family of non-selective Ca+2 channels known as transient receptor potential channels. High-sucrose (HS)-fed animals with hyperglycaemia and dyslipidaemia, were accompanied by increased body mass index. mesenteric adipose tissue accumulation with larger diameter cells and hepatic steatosis in comparison to those fed normal diet. HS mice also exhibited enhanced adipose, liver, and pancreas TNFα and VEGF levels. ML204 exacerbated hyperglycaemia, dyslipidaemia, fat tissue deposition, hepatic steatosis, and adipose tissue and liver TNFα in HS-fed mice. Normal mice treated with the blocker had greater hepatic steatosis and adipose tissue cell numbers/diameter than those receiving vehicle, but showed no significant changes in tissue inflammation, glucose, and lipid levels. The results indicate that TRPC4/TRPC5 protect against the metabolic imbalances caused by HS ingestion.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1424-8247 1424-8247
DOI:	10.3390/ph16081100