ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2020) 17 15.11 | DOI: 10.1530/ey.17.15.11

ESPEYB17 15. Editors’ choice (1) (18 abstracts)

15.11. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis

Chaurasia B, Tippetts TS, Mayoral Monibas R, Liu J, Li Y, Wang L, Wilkerson JL, Sweeney CR, Pereira RF, Sumida DH, Maschek JA, Cox JE, Kaddai V, Lancaster GI, Siddique MM, Poss A, Pearson M, Satapati S, Zhou H, McLaren DG, Previs SF, Chen Y, Qian Y, Petrov A, Wu M, Shen X, Yao J, Nunes CN, Howard AD, Wang L, Erion MD, Rutter J, Holland WL, Kelley DE & Summers SA



To read the full abstract: Science 2019;365:386–392.

By genetically engineering mice, the authors deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets

Sphingolipids such as ceramides and dihydroceramides are products of fat and protein metabolism that accumulate in subjects with obesity and hyperlipidemia. These lipids have been implicated in a wide range of cellular processes related to metabolism, growth, and survival. Previous research suggested associations between serum and tissue levels of ceramides and comorbidities of obesity, including insulin resistance, type 2 diabetes (T2D), and major adverse cardiac events. This article claims that ceramides are the major contributor to insulin resistance and fatty liver disease. The mechanism is related s to the enzyme dihydroceramide desaturase 1 (DES1).

Some clinics have begun using serum ceramide levels as a measure of cardiovascular disease risk. Here, they studied the role of these sphingolipids as causative agents in the development of insulin resistance and hepatic steatosis. Clinical studies demonstrate inverse correlations between the amounts of ceramides in plasma and adiponectin in healthy individuals or those with T2D.

Inhibition of DES1 may provide a means of treating hepatic steatosis and metabolic disorders and provide evidence that therapeutically intervening in the ceramide biosynthesis pathway in mice can improve metabolic homeostasis.

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