Leptin was discovered only in 1994. It is produced and secreted mostly by fat tissue, gastric epithelial cells and placental cells and affects metabolism, weight, bone and ovulation. Leptin is a hormone released by fat tissue, and the level in serum is equal to the amount of fat that the animal had. The lower an animal's body fat is or the less energy-efficient it is (eg, hungry), the lower its serum leptin content will be - which would in turn make the animal more active in foraging and less energetically dependent on itself. The other way around is that the higher an organism's body fat, the higher the leptin content of their serum, which then reduces eating and speeds up metabolism. This is the kind of negative feedback loop by which leptin keeps an organism in energy and weight balance. Leptin is a hormone that regulates your energy and weight. Because of its metabolic and appetite interplay, it's been studied for obesity and obesity disorders.
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Effects of Leptin on Health
Leptin is a hormone released by fat cells that is mostly responsible for body weight and energy levels. Leptin's main function is to send data about the body's fat stores to the brain, which in turn drives appetite and metabolism. Leptin curbs the hunger pangs and drives up metabolic rate. The higher fat stores, the higher the levels of leptin that tell the brain to starve. But others become recalcitrant to leptin and gain weight.
Metabolic Syndrome
Leptin resistance goes hand in hand with metabolic syndrome - obesity, hypertension, high blood sugar, and high blood fat. Leptin is high, but the body doesn't respond to its signals well, and you can't control appetite or weight.
Inflammation and Immune Response
It's not just inflammation that Leptin plays into. Leptin can be high for chronic inflammation - the predisposition to a host of illnesses, including cardiovascular disease, diabetes and certain cancers.
Fertility and Menstrual Cycle
Leptin also influences fertility in women. Male adult leptin is 10%-50% of female levels, and high levels of leptin impair testicular function. The obesity epidemic has uncovered the leptin resistance circuitry and over-reacting to leptin can be infertile for men and women alike. With the right level of leptin you manage your period and fertility.
Mental Health
Research has also shown that leptin may be linked to mental health. Changes in leptin levels may affect mood, potentially contributing to the development of depression and anxiety.
Fig. 1 Schematic diagram of the effect of leptin on reproduction (Childs, G., et al. 2021).
LEPR Signaling Pathways
The cellular signalling cascades that are engaged by the long isoform LEPRb are mainly Janus kinases (JAKs) and signal transducers and activators of transcription (STAT3 and STAT5). But then STAT5 turned out to be associated with fertility. But knockout of STAT5 and/or STAT3 in LEPR cells leads to normal puberty, cyclicity and fertility in just 4 months, so HPG target cells might modulate leptin signalling via multiple signalling pathways. These are leptin-mediated signalling pathways via mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1/2; phosphoinositide 3-kinases (PI3K), mammalian target of rapamycin (mTOR) and/or nitric oxide. Scientists who look at individual target cells in the HPG axis have tested all of these pathways to see which ones drive leptin.
Regulate Leptin Levels
- Balanced Diet: Eat a diet high in fiber and low in processed foods.
- Regular Exercise: Getting exercise regularly can increase leptin sensitivity and healthy weight management.
- Sleep: Sleep is necessary for hormone balance, and sleep deprivation will result in leptin malfunction.
- Absorb Stress: When stress is lowered, your hormones, such as leptin, will remain stable.
Sites of Leptin Action
Leptin flows in the blood and binds to receptors in tissues such as the liver, pancreas and skeletal muscle, but acts mainly through the hypothalamus (specifically the arcuate nucleus). Leptin regulates energy balance by triggering the systems that regulate appetite suppression and energy use. Leptin can activate sympathetic nerves and activate adrenergic receptors in the walls of fat cells to use up energy. Leptin also directly attacks liver and muscle cells to oxidise fatty acids and burn away fat. Leptin presence isn't only about satiety control - it influences neuronal structure, synaptic plasticity and cognition. Because leptin signalling and brain circuits are complex, their significance to neurological function and pathology is unquestionable.
Leptin as an Anti-Obesity Hormone
Leptin is an anti-obesity hormone that keeps your body budgeted for energy, fat and satiety. Leptin-signalling dysfunction also leads to leptin resistance - what we see in obesity and metabolic syndrome.
Leptin drops when you fast or are deprived of energy, so energy isn't being re-energised. It's a adaptive response that wreaks havoc on mechanisms designed to conserve energy, make efficient use of nutrients and make life possible when we're running out of it.
Development of Weight Loss Drugs
Leptin affects appetite regulation and energy metabolism by binding to leptin receptors in the hypothalamus. Related weight loss drugs include Leptin and Leptin receptor agonists, NPY antagonists, MC receptor agonists, UCPs agonists, β3-AR agonists, GLP-1 receptor agonists, etc. Many obese patients show leptin resistance despite having high levels of leptin in their bodies. At this time, leptin cannot work effectively, so the effect of using leptin alone for weight loss is limited. This discovery poses a challenge to the basic research and drug development of leptin. Researchers are exploring the possibility of combining leptin with other therapies (such as GLP-1 receptor agonists, insulin, etc.) in order to enhance the weight loss effect. Leptin drugs on the market are still in the research and development stage, and clinical trials focus on exploring their safety and effectiveness.
Conclusion
Leptin is one of many signalling hormones and neurons coordinating energy metabolism and weight. Leptin effects metabolism, inflammation, fertility and wellbeing. Its primary function is to communicate data about body fat stores to the brain, and in turn to drive appetite and metabolism. Leptin - an engine of potential weight-loss drugs - has multiple biological ramifications and multiple research streams. The possibilities of leptin will still offer up promising solutions for treating obesity in the future.
References
- Childs, G., et al. The importance of leptin to reproduction. Endocrinology. 2021, 162(2): 204-215.
- Obradovic, M., et al. Leptin and obesity: role and clinical implication. Frontiers in endocrinology. 2021, 12: 585887.
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