Tag: leptin

Study Implicates High Leptin Levels in Androgen Deficiencies

Source: National Cancer Institute on Unsplash

Researchers have uncovered new clues about the cellular processes that can lead to androgen deficiencies, in which high leptin levels appear to play a role. The findings are published in the journal Cell Death & Disease.

Symptoms of testosterone deficiency include low sex drive, erectile dysfunction, depression, and fatigue. TD afflicts approximately 30% of men aged 40-79 years, with an increase in prevalence strongly associated with ageing and common medical conditions including obesity, diabetes, and hypertension.

“Although testosterone deficiency may be present in one in five men 40 years or older, the driving factors remain largely unknown,” said Himanshu Arora, PhD, assistant professor of urology.

Dr Arora’s lab examined the effect of different concentrations of leptin on the microenvironment of the testes. The research builds on prior studies of how Sertoli and peritubular myoid cells (PMC) in the testicular microenvironment help drive Leydig stem cell differentiation via the cellular desert hedgehog signalling pathway, which transmits information to embryonic cells that guides proper cell differentiation.

The researchers extracted cellular samples from men undergoing testes biopsies for sperm retrieval. When the testes microenvironment secreted leptin in low doses, they found that Leydig stem cells differentiated into adult Leydig cells producing normal levels of testosterone. Higher doses of leptin were observed to depress testosterone levels.

“Our findings identify leptin as a key factor within the testes microenvironment,” said Dr Arora, adding that the insight “holds important implications for androgen deficiency and could have further application in prostate cancer research.”

Noting that leptin is already used in treating patients for obesity, “Preclinical studies could indicate whether adjusting levels of this hormone would be helpful in patients with testosterone deficiency,” said Ranjith Ramasamy, MD, study co-author and associate professor and director of the Miller School’s Reproductive Urology Program.

Source: University of Miami Health System, Miller School of Medicine

Low Leptin Levels Can Stifle Response to Vaccines

Image source: NCI on Unsplash

Reduced levels of leptin, a metabolic hormone, is linked to poor vaccine antibody responses in the general population, according to research by the University of Queensland.

The researchers made the discovery while investigating the response of several cohorts to the influenza vaccine or hepatitis B vaccine prior to COVID.

Professor Di Yu at the University of Queensland identified a link between the metabolic and immune systems that could be exploited to develop new strategies for improving vaccine protection in vulnerable populations.

“Using multiple advanced techniques in immunology, genetics and biochemistry, our study found leptin directly promoted the development and function of cells which are vital in triggering an antibody response,” Professor Yu said.

“In collaboration with global teams, we identified the reduction of an essential metabolic hormone called leptin was associated with compromised vaccine responses in both young and older individuals.

“As a result, we can now identify those who are at risk of not generating an antibody response after vaccination.”

Leptin is a metabolic hormone mostly produced by fat tissue.

“Vaccines have been known for a very long time to have a different efficacy for individuals,” he said.

“Although our genetics partially contribute to the difference, other factors are also essential. When we are fit and healthy, we have a much better vaccine efficacy.

“If we are healthy, we have a good metabolism and a normal level of leptin, but if we have malnutrition or some disease conditions, we may have a low level of leptin, which may limit our vaccine response and immune protection.”

Professor Yu said that one subject was future research was that many people with obesity and high levels of leptin conversely often had leptin resistance, which could also potentially lead to a poorer vaccine response.

The researchers are hoping to test responses to the COVID vaccines to find biomarkers that could identify people who may not mount a strong vaccine response.

“During the era of the COVID pandemic, the successful vaccination for SARS-CoV-2 is the major hope to bring society back to normalcy. Differing vaccine responses cause a major bottleneck in large-scale vaccination programs,” said Professor Yu.

Source: News-Medical.Net

.Journal information: Deng. J., et al. (2021) The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses. Nature Communications. doi.org/10.1038/s41467-021-23220-x.

Study Reveals More Secrets of Leptin’s Role in Appetite Control

A new study describes how leptin, an appetite-suppressing hormone released from adipose tissue, is involved in appetite suppression through the dopamine pathway.  

Since the discovery of leptin in the 1990s, many questions still remain over how it suppresses appetite. Now, a new study in mice describes novel neurocircuitry between midbrain structures that control feeding behaviours under the modulatory control of leptin.

Leptin links the body and the brain, providing information about its metabolic state and influencing energy balance. Animals deficient for leptin rapidly become obese without its regulatory control of feeding behaviour, showing just how important it is.

“This process is shaped by communication between bodily fat storages (via a hormone called leptin) and the brain’s dopamine reward system. This leptin-dopamine axis is critically important for body weight control, but its modes of action were not well understood,” said Roger Adan, PhD, Department of Translational Neuroscience, University Medical Centre Utrecht.

Not only does leptin suppress eating through signals to brain regions controlling eating behaviours, but it also lowers food’s reward value in the brain’s dopamine (DA) reward system. That food-reward pathway was known to involve dopaminergic neurons of the ventral tegmental area (VTA) signaling to the nucleus accumbens (NAc). However, these DA neurons do not have receptors for leptin.

The researchers mapped the new microcircuitry with a combination of technologies, including optogenetics, chemogenetics and electrophysiology.

“Although leptin receptors are present on [some] dopamine neurons that signal food reward, we discovered that leptin receptors are also present on inhibitory neurons that more strongly regulate the activity of dopamine neurons. Some of these inhibitory neurons suppressed food seeking when [animals were] hungry, whereas others [did so] only when [animals were] in a sated state,” said Professor Adan, also of the Department of Translational Neuroscience, University Medical Center Utrecht and University Utrecht.

John Krystal, MD, Editor of Biological Psychiatry, said of the study, “It turns out that leptin plays key modulatory roles in an elegant circuit that unites midbrain and limbic reward circuitry. By inhibiting hypothalamic neurons and ultimately suppressing the activity of dopamine neurons in the midbrain that signal reward and promote feeding, leptin reduces food intake in animals under conditions when caloric intake has exceeded energy use.”

Professor Adan concluded that, “Targeting these neurons may provide a new avenue for the treatment of anorexia nervosa and to support dieting in people with obesity.”

Source: News-Medical.Net

Journal information: Omrani, A., et al. (2021) Identification of novel neurocircuitry through which leptin targets multiple inputs to the dopamine system to reduce food reward seeking. Biological Psychiatry. doi.org/10.1016/j.biopsych.2021.02.017.