Ablation of the very-long-chain fatty acid elongase ELOVL3 in mice leads to constrained lipid storage and resistance to diet-induced obesity.

• Although saturated and monounsaturated very-long-chain fatty acids (VLCFAs) have long been associated with undesirable effects on health, including obesity, heart failure, and atherosclerosis, the physiological role of endogenous synthesis is largely unknown. The fatty acid elongase ELOVL3 is involved in the synthesis of C20-C24 saturated and monounsaturated VLCFAs mainly in liver, brown and white adipose tissue, and triglyceride-rich glands such as the sebaceous and meibomian glands. Here we show that ablation of ELOVL3 leads to reduced adiponectin levels, constrained expansion of adipose tissue, and resistance against diet-induced obesity, a situation that is more exaggerated in female mice. Both female and male knockout mice show reduced hepatic lipogenic gene expression and triglyceride content, a situation that is associated with reduced de novo fatty acid synthesis and uptake. As a consequence, the VLDL-triglyceride level in serum is significantly reduced. Remarkably, despite increased energy expenditure, markedly reduced serum levels of leptin, and increased expression of orexigenic peptides in the hypothalamus, the Elovl3(-/-) mice do not compensate by increased food intake. Thus, these results reveal that C20-C22 saturated and monounsaturated VLCFAs produced by ELOVL3 are indispensable for appropriate synthesis of liver triglycerides, fatty acid uptake, and storage in adipose tissue.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

NATURVETENSKAP  -- Biologi -- Zoologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Zoology (hsv//eng)

Nyckelord

Acetyltransferases

genetics

metabolism

Adipokines

secretion

Adiponectin

blood

Adipose Tissue

metabolism

Animals

Basal Metabolism

genetics

Cells

Cultured

Diet

Eating

genetics

Female

Gene Expression Regulation

Enzymologic

Lipogenesis

genetics

Lipoproteins

VLDL

biosynthesis

blood

Liver

metabolism

Male

Mice

Mice

Inbred C57BL

Mice

Knockout

Obesity

enzymology

metabolism

Sex Factors

Triglycerides

biosynthesis

blood

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)