Study: Liver responds positively to leptin treatment in patients with lipodystrophy

April 4, 2017, University of Michigan

Researchers at Michigan Medicine have found the livers of patients with a rare disease that affects metabolism have responded positively to leptin therapy.

In an open-label study, funded by the National Institutes of Health, the research team predicted the response of 23 patients with partial -associated nonalcoholic steatohepatitis (fatty liver) to metreleptin, a man-made version of the naturally occurring hormone leptin, which regulates fat and glucose metabolism.

The researchers reported patients with a lower baseline leptin level had a higher response rate after one year of treatment with metreleptin, a pharmaceutical produced by Novelion Therapeutics' subsidiary. They presented their findings today at ENDO 2017, the annual meeting of the Endocrine Society, in Orlando, Florida.

Lipodystrophy is a group of rare diseases that share in common the selective loss of fat tissue from the body. Patients affected by the diseases generally have severe insulin resistance, high lipids in their blood and fatty liver. The condition highlights how important fat cells are to regulating a person's metabolism.

Generalized lipodystrophy results in throughout the entire body. Partial lipodystrophy results in fat loss typically in the arms, legs, head and torso, and fat accumulation in the neck, face and intra-abdominal areas of the body. Metreleptin was approved by the Food and Drug Administration in 2014 to treat generalized lipodystrophy, but has not been approved to treat partial lipodystrophy.

"Fatty liver, or excess fat building up in the liver, is a common metabolic disturbance seen in patients with lipodystrophy," says Elif Oral, M.D., associate professor of endocrinology at Michigan Medicine and principal investigator of the study. "The underlying metabolic disturbances seen in this patient population can be difficult to manage with traditional therapies."

The partial lipodystrophy study participants underwent two liver biopsies, one at the beginning of the trial and after one year of treatment. Investigators observed their NASH score, a numerical score for progression of fatty liver disease in patients, and their NAS score, a numerical score for progression of non-alcoholic fatty liver disease.

Of the 23 patients enrolled in the study, 22 were treated with at least one dose of metreleptin at baseline. Of the 18 patients who completed treatment after one year, NASH scores improved from a mean of 6 at baseline (showing moderate to advanced disease) to a mean of 5. NAS scores also improved from a mean of 5 at baseline to a mean of 4 after 12 months of treatment.

The researchers noted that these changes were statistically significant in the patient group.

"About half of the patients had scores that lowered by two points or more, which is clinically significant in patients with this disease," says Oral. "Generally, that type of drop is only seen with 10 percent or more sustained weight loss in the common form of , which usually only occurs with metabolic surgery."

Patients that experienced the two-point or greater reduction improvement in their scores from treatment had a lower baseline leptin level of 14.5 ng/mL versus non-responders whose average leptin level at baseline was 25 ng/mL.

In addition, some patients saw reductions in glucose control and lipid levels, but the differences noted in the entire cohort did not attain statistical significance. The most frequently reported adverse events in the study, occurring in more than 20 percent of the patients, were upper respiratory infections, hypoglycemia and diarrhea.

"The liver disease at baseline is quite significant among the in this study, which showed a significant degree of inflammation and fibrosis, even in the absence of test abnormalities," says Nevin Ajluni, M.D., assistant professor of endocrinology at Michigan Medicine and the presenting author of the study. "This highlights the importance of screening for this complication."

Explore further: Cholesterol drug shown to reduce inflammation, other factors in patients

Related Stories

Cholesterol drug shown to reduce inflammation, other factors in patients

March 24, 2017
Statin drugs are widely used to manage high cholesterol and reduce the risk of cardiovascular disease. But in a new review of more than 50 studies, researchers cite reductions in liver inflammation and improvements in other ...

Drug that reduces abdominal fat in HIV patients also may reduce fat in liver

July 19, 2014
The only drug to receive FDA approval for reduction of the abdominal fat deposits that develop in some patients receiving antiviral therapy for HIV infection may also reduce the incidence of fatty liver disease in such patients. ...

Single-stage procedure treats cellulite, lipodystrophy

January 27, 2016
(HealthDay)—A single-stage procedure can provide simultaneous treatment for cellulite and lipodystrophy, according to a clinical report published in the January issue of Lasers in Surgery and Medicine.

Diet and exercise can improve kidney function in patients with fatty liver disease

November 21, 2016
Non-alcoholic steatohepatitis (NASH) is a potentially serious liver condition characterized by excess fat in the liver associated with inflammation and scarring. NASH may progress to cirrhosis of the liver and liver cancer, ...

Non-alcoholic fatty liver disease shown to affect the development of coronary artery calcification

April 23, 2015
Data revealed today at The International Liver Congress 2015 show that non-alcoholic fatty liver disease (NAFLD) plays a role in the early stages of coronary atherosclerosis and in its more severe form it can also promote ...

Fatty liver: Turning off TAZ reverses disease

October 27, 2016
Scientists at Columbia University Medical Center (CUMC) have identified a factor in liver cells that is responsible for turning a relatively benign liver condition, present in 30 percent of U.S. adults, into a serious disease ...

Recommended for you

First proof a synthesized antibiotic is capable of treating superbugs

March 23, 2018
A "game changing" new antibiotic which is capable of killing superbugs has been successfully synthesised and used to treat an infection for the first time—and could lead to the first new class of antibiotic drug in 30 years.

Scientists identify potential drug target in blood-feeding hookworms

March 22, 2018
In hookworms that infect and feed on the blood of mice, scientists have discovered a key step in blood digestion that can be targeted to disrupt the parasite's development and survival. These findings, published in PLOS Pathogens ...

Global burden of low back pain—a consequence of negligence and misinformation

March 21, 2018
A series of groundbreaking papers from Australian and international researchers in The Lancet, published today (22/3) warns that low back pain is a major health burden globally - across developed and developing nations - ...

Microscopic 'shuttles' transport enzyme from cells to trigger onset of kidney disease

March 21, 2018
A new study involving the University of Sheffield has identified a key culprit in the onset of kidney disease in a major marker for kidney disease development.

Metabolite therapy proves effective in treating C. difficile in mice

March 20, 2018
A team of UCLA researchers found that a metabolite therapy was effective in mice for treating a serious infection of the colon known as Clostridium difficile infection, or C. difficile.

Study of COPD patients has created a 'looking glass' into genome of pathogen

March 19, 2018
Decades of work on chronic obstructive pulmonary disease (COPD) at the University at Buffalo and the Veterans Affairs Western New York Healthcare System have yielded extraordinary information about the pathogen that does ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.