Impaired lipolysis leads to severe metabolic disorder

Impaired lipolysis leads to severe metabolic disorder

(HealthDay)—Genetic mutation causing interference with encoding of hormone-sensitive lipase (HSL) results in susceptibility to metabolic disorders, according to research published online May 21 in the New England Journal of Medicine.

Jessica S. Albert, Ph.D., of the University of Maryland in Baltimore, and colleagues used genetic sequencing in Old Order Amish participants with fasting serum triglyceride levels at the lower and upper extremes of the distribution. The authors sought to identify a mutation in the gene encoding HSL, a key enzyme for lipolysis. The researchers also obtained biopsy specimens of adipose tissue from participants who were homozygous (DD genotype), heterozygous (ID genotype), or noncarriers (II genotype) for the deletion mutation.

The researchers found that carriers of the deletion mutation in the gene encoding HSL had dyslipidemia, hepatic steatosis, systemic insulin resistance, and diabetes. Absence of HSL protein, small adipocytes, impaired lipolysis, insulin resistance, and inflammation were observed in from participants with the DD genotype. Down-regulation of transcription factors responsive to peroxisome-proliferator-activated receptor γ and downstream target genes in those with the DD genotype was associated with altered regulation of pathways influencing adipogenesis, insulin sensitivity, and lipid metabolism.

"These findings indicate the physiological significance of HSL in adipocyte function and the regulation of systemic lipid and glucose homeostasis and underscore the severe metabolic consequences of impaired lipolysis," the authors write.

More information: Abstract
Full Text

add to favorites email to friend print save as pdf

Related Stories

Gene behind unhealthy adipose tissue identified

May 22, 2014

Researchers at Karolinska Institutet in Sweden have for the first time identified a gene driving the development of pernicious adipose tissue in humans. The findings imply, which are published in the scientific ...

Pot smoking linked to some metabolic changes

Apr 19, 2013

(HealthDay)—Regularly smoking pot is associated with visceral adiposity and adipose tissue insulin resistance, but not other metabolic changes such as impaired β-cell function or hepatic steatosis, according ...

Genes may thwart seniors' exercise gains

Mar 14, 2014

Keeping strong and physically fit is crucial to maintaining independence among the elderly. Exercise has repeatedly been shown to reduce or slow age-related declines in physical function and is a widely recommended for seniors, ...

Recommended for you

Stem cells from nerves form teeth

1 hour ago

Researchers at Karolinska Institutet in Sweden have discovered that stem cells inside the soft tissues of the tooth come from an unexpected source, namely nerves. These findings are now being published in the journal Nature and co ...

Human brain has coping mechanism for dehydration

15 hours ago

(HealthDay)—Although dehydration significantly reduces blood flow to the brain, researchers in England have found that the brain compensates by increasing the amount of oxygen it extracts from the blood. ...

User comments