The Contribution of Liver 3-Methylglutaryl-CoA Synthase 2 (HMGCS2) to Dietary Medium- Chain Triglyceride-Induced Ketone Body Production

Presenter's Name(s)

Kate Zoller

Conference Year

2024

Abstract

Asthma is characterized by overactive responsiveness to triggers that cause airway narrowing and difficulty breathing. Ketone bodies, such as -hydroxybutyrate (BHB), decrease this response. BHB is produced in the liver by the enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2). Inducible liver-specific Hmgcs2-deficient and control mice were evaluated for their responses to feeding interventions that are associated with decreased airway narrowing in asthma. Fasting, ketogenic diet, and medium-chain triglycerides all increased BHB concentrations in control mice, whereas BHB was not elevated in liver Hmgcs2-deficient mice. These results support this mouse model’s utility for examining the necessity of BHB in decreasing asthma-associated airway narrowing.

Primary Faculty Mentor Name

Matthew Poynter

Graduate Student Mentors

Maddie Mank

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Biology

Primary Research Category

Life Sciences

Abstract only.

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The Contribution of Liver 3-Methylglutaryl-CoA Synthase 2 (HMGCS2) to Dietary Medium- Chain Triglyceride-Induced Ketone Body Production

Asthma is characterized by overactive responsiveness to triggers that cause airway narrowing and difficulty breathing. Ketone bodies, such as -hydroxybutyrate (BHB), decrease this response. BHB is produced in the liver by the enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2). Inducible liver-specific Hmgcs2-deficient and control mice were evaluated for their responses to feeding interventions that are associated with decreased airway narrowing in asthma. Fasting, ketogenic diet, and medium-chain triglycerides all increased BHB concentrations in control mice, whereas BHB was not elevated in liver Hmgcs2-deficient mice. These results support this mouse model’s utility for examining the necessity of BHB in decreasing asthma-associated airway narrowing.