Innovative hormone treatment significantly reduces the risk of metabolic diseases

[Nov. 16, 2022: Nina Haas, Medical University of Vienna]


Sitting too much is not the same as exercising too little. (CREDIT: Getty Images)


A study group at MedUni Vienna has identified a regulatory loop controlled by leptin, by which this adipocyte-derived hormone regulates hepatic lipid metabolism via the autonomic nervous system.


The study provides evidence that this adipose tissue-brain-liver axis, previously identified in animal models, also exists in humans and is opening up new approaches for treating metabolic diseases such as fatty liver disease.


 
 

The aim of the study conducted by Thomas Scherer and Matthäus Metz from the Division of Endocrinology and Metabolism (Department of Medicine III at MedUni Vienna and Vienna General Hospital) was to identify the effects of leptin on liver fat metabolism in humans, which are independent of its anorexic actions.


The adipose tissue hormone leptin circulates in the blood in relation to fat mass and acts primarily as a satiety signal in the brain. In addition to controlling appetite, it is also involved in the regulation of glucose and lipid metabolism. These effects are mediated through the autonomic nervous system, which links the brain to peripheral organs, such as the liver and the adipose tissue.


 

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Human recombinant leptin (metreleptin) is approved for the treatment of lipodystrophy. In these leptin-deficient patients, metreleptin lowers hepatic lipid content independent of food intake. However, the underlying mechanism was unclear so far.


In previous animal experiments, the study group demonstrated that leptin stimulates the release of lipids from the liver and at the same time suppresses the formation of new lipids, thereby reducing liver fat content. This effect was dependent on an intact autonomic innervation of the liver and was abolished after severing the vagus nerve.


 
 

In the present study, the authors tested whether a comparable mechanism regulates hepatic lipid metabolism in humans. They show that a single injection of metreleptin stimulated the hepatic lipid export of healthy, normal-weight men and lowered liver fat content.


Researchers propose that leptin has anti-steatotic properties that are independent of food intake by stimulating hepatic VLDL-TG export via a brain-vagus-liver axis. (CREDIT: Cell Metabolism)


A similar effect occurred after modified sham feeding, a procedure that induces cephalic phase reflexes and thereby physiologically stimulates the vagus nerve. In contrast, metreleptin failed to promote hepatic lipid secretion in liver transplant recipients whose livers are not innervated by the autonomic nervous system as a result of transplantation.


 
 

The study therefore suggests that leptin also regulates liver fat content in humans via the brain and the autonomic nervous system, explained study leader Thomas Scherer: "Our results suggest that leptin, similar to previous observations in animal models, also stimulates the release of lipids from the liver in humans and thus lowers liver fat via the central nervous system and the vagus nerve."


The study was conducted by Thomas Scherer and Matthäus Metz from the Division of Endocrinology and Metabolism (Department of Medicine III at MedUni Vienna and Vienna General Hospital)


The researchers thus hypothesise that leptin may prevent the development of fatty liver independent of its appetite-inhibiting effects. In addition, the study suggests that the brain has an influence on liver fat metabolism via the autonomic nervous system in humans.


 
 

This could open up new treatment options involving the central nervous system for the prevention of the widespread fatty liver disease.



What are normal leptin levels?


Normal value ranges for leptin levels may vary slightly among different laboratories. Be sure to look at the range of normal values listed on your laboratory report or ask your healthcare provider if you have questions about your results.


In general, normal ranges for leptin levels include:

  • Adults assigned female at birth: 0.5 - 15.2 nanograms per milliliter (ng/mL).

  • Adults assigned male at birth: 0.5 - 12.5 ng/mL.

  • What happens when leptin levels are too high?

  • Since the amount of leptin in your blood is directly proportional to the amount of adipose tissue (body fat), having obesity results in high levels of leptin (hyperleptinemia). This can cause a lack of sensitivity to leptin, a condition known as leptin resistance.


 
 

Other conditions associated with hyperleptinemia include:

  • Nonalcoholic fatty liver disease.

  • Rabson–Mendenhall syndrome.

  • Neurodegenerative disorders.

  • Depression.

  • Food addiction.



What happens when leptin levels are too low?


It’s very rare to have lower-than-normal leptin levels (hypoleptinemia). The main condition associated with low leptin levels is called congenital leptin deficiency, which is a genetic condition you’re born with that prevents your adipose tissue from producing leptin.


Without leptin, your body thinks it has no body fat, which then signals intense, uncontrolled hunger and food consumption.


 
 

Because of this, congenital leptin deficiency results in class III obesity in children and delayed puberty. It’s also associated with the following conditions:

  • Frequent bacterial infections.

  • Hyperinsulinemia (excess insulin production).

  • Fatty liver disease.

  • Dyslipidemia (an imbalance of lipids, including cholesterol and triglycerides).

  • Hypogonadotropic hypogonadism (low sex hormone levels).




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Note: Materials provided above by Medical University of Vienna. Content may be edited for style and length.


 
 

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