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Posts Tagged ‘leptin receptor’


The Biologic Roles of Leptin in Metabolism, Leptin Physiology and Obesity: On the Mechanism of Action of the Hormone in Energy Balance

Reporter: Aviva Lev-Ari, PhD, RN

 

More than $140 billion is spent each year in the United States to treat obesity-related diseases, according to the CDC.

Worldwide obesity rates have doubled since 1980, and most people now live in countries where more deaths are caused by overweight and obesity than by malnourishment, according to the World Health Organization.

Treatment with leptin was approved in the United States in 2014 for use in congenital leptin deficiency as well as in an unusual syndrome of lipodystrophy, but the protein has not been readily available for clinical experiments.

These are the conclusions in a commentary published June 22 in Cell Metabolism by Harvard Medical School metabolism experts Jeffrey Flier and Eleftheria Maratos-Flier.

Flier, the HMS George Higginson Professor of Physiology and Medicine, and Maratos-Flier, HMS professor of medicine at Beth Israel Deaconess Medical Center, have made significant contributions to the understanding of the metabolism of obesity and starvation in general, and of leptin in particular.

The role for leptin as a starvation signal is now well established. [T]he physiologic role of leptin in most individuals may be limited to signaling the response to hunger or starvation, and then reversing that signal as energy stores are restored

Conclusion

“We continue to believe that healthy and lean individuals exist who resist obesity at least in part through their leptin levels, and that some individuals develop obesity because they have insufficiently elevated leptin levels or cellular resistance to leptin,” Flier said.

“But in science, belief and knowledge are two different things, and as much as we may lean toward this belief, we ought to develop evidence for this hypothesis or abandon it in favor of new potential mechanisms for the regulation of body weight,” he said.

SOURCES

Leptin’s Physiologic Role: Does the Emperor of Energy Balance Have No Clothes?

Jeffrey S. Flier'Correspondence information about the author Jeffrey S. Flier

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Eleftheria Maratos-Flier
Publication stage: In Press Corrected Proof

Seeking evidence for anti-obesity claim – Does the Emperor Have Clothes?

Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity

Maren Leifheit-Nestler12, Nana-Maria Wagner13, Rajinikanth Gogiraju1,Michael Didié14, Stavros Konstantinides15, Gerd Hasenfuss1and Katrin Schäfer1*

J Translational Medicine: Cardiovascular, Metabolic and Lipoprotein Translation. 2013; 11:170.  http://www.translational-medicine.com/content/11/1/170

http://dx.doi.org/10.1186/1479-5876-11-170

 

Other related articles on LEPTIN published in this Open Access Online Scientific Journal include the following:

 

Leptin signaling in mediating the cardiac hypertrophy associated with obesity

Larry H Bernstein, MD, FCAP, Reviewer, and Aviva Lev-Ari, PhD, RN

 

Leptin and Puberty

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Pregnancy with a Leptin-Receptor Mutation

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

New Insights into mtDNA, mitochondrial proteins, aging, and metabolic control

Curator: Larry H. Bernstein, MD, FCAP

Adipocyte Derived Stroma Cells: Their Usage in Regenerative Medicine and Reprogramming into Pancreatic Beta-Like Cells

Curator: Evelina Cohn, PhD

Fat Cells Reprogrammed to Make Insulin

Curator: Larry H. Bernstein, MD, FCAP

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Leptin is considered to have an important role in reproductive functions, including menstrual-cycle regulation, pregnancy, and lactation. The absence of leptin action caused by functional mutations in the leptin gene (LEP) or the leptin receptor gene (LEPR) has been linked to infertility in rodents and humans. A pregnancy was reported in a woman despite absent leptin signaling.

In 1998, it was reported the case of a morbidly obese patient with a rare homozygous LEPR mutation, which was shared by several affected siblings. The mutation was found in the patient’s blood and adipose tissue, indicating no evidence of chimerism. She had been followed for morbid obesity since early childhood, with abnormal compulsive-feeding behaviors and reduced levels of growth hormone and thyrotropin. She entered puberty late, with irregular cycles after the age of 17 years. Repeated evaluations of sex-hormone levels were considered to be normal after the age of 18 years. The patient underwent abdominoplasty at the age of 16 years and gastric-bypass surgery at the age of 24 years. Six months after gastric bypass, her weight had decreased from 220 kg (485 lb) to 170 kg (375 lb), with a concurrent decrease in the body-mass index (the weight in kilograms divided by the square of the height in meters) from 81 to 62. She was counseled regarding contraception and was prescribed oral contraceptives. Two years after gastric bypass, just before an unplanned pregnancy, she had no diabetes, hypertension, respiratory disorders, or other recognized complications of obesity.

Ultrasonographic examinations during pregnancy were considered normal except for suspected macrosomia in the third trimester. The patient’s total weight gain during pregnancy was 50 kg (110 lb) from a prepregnancy weight of 180 kg (397 lb). Routine screening for gestational diabetes was normal. Although occasional elevated blood sugar levels were documented during the pregnancy, the glycated hemoglobin level in the third trimester was 5.6%. At 37 weeks 5 days of gestation (on the basis of first-trimester ultrasonography), the patient delivered a son by elective cesarean section, which was performed because of breech presentation and suspected macrosomia under epidural anesthesia after the administration of glucocorticoids for fetal lung maturation. The birth weight was 3720 g (8.2 lb), and the length was 50 cm (19.7 in.); the head circumference was 36.5 cm (14.4 in.), which was above the 90th percentile. The patient’s postpartum course was complicated by a wound infection. The infant’s neonatal course was complicated by hypoglycemia, hypocalcemia, and jaundice requiring phototherapy. The patient briefly breast-fed her child. The child’s growth and development have been normal; his weight at 1 year was 14 kg (31 lb).

This case of a natural pregnancy in a woman with a homozygous LEPR mutation calls into question the belief that leptin function is critical to reproductive function.

 

Source References:

 

http://www.nejm.org/doi/full/10.1056/NEJMc1200116

 

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