Everyone is talking about hormones related to metabolism. Let's review Leptin focusing on its function and dysfunction. I will cover GLP-1 and adiponectin another time.
First discovered in 1994, leptin is a hormone secreted by white adipose or fat tissue. It plays an important role in feedback from fat cells to the hypothalamus in the brain and provides a satiety or a satisfied feeling after eating. When your leptin levels are low, you will typically become hungry. After eating, your leptin levels rise, telling your brain that it's time to stop eating. Leptin also tells the body it is time to mobilize fat stores for energy.
Problems occur when the message is not received in the brain. This can happen with leptin resistance (LR). When leptin resistance occurs, one has very high levels of leptin most of the time. This over-signaling results in the hypothalamus down-regulating receptors to turn down the message. The brain interprets the high leptin levels as fat cells crying wolf. The results in a further increase in leptin occur to tell the brain it is satisfied and to stop eating. High levels of leptin should also tell the body it's time to burn fat instead of storing it, and this does not occur when LR is present. Getting excess weight off in the face of LR is almost impossible.
What are some of the causes of LR, and what is happening with other hormones in the body?
Disrupted sleep. A study in mice showed that after 3 days of fragmented sleep, mice exhibited overeating behaviors and weight gain.1 Initially, their leptin levels went down but then went up higher than the baseline. This study and others have shown that not getting enough good-quality sleep results in abnormal weight gain and leptin is one of the hormones that is involved.
Insulin, cortisol, triglycerides. Once LR occurs, obesity is inevitable. Obesity triggers insulin resistance (IR), and IR further triggers obesity. Obesity results in increased levels of cortisol, and cortisol further works to increase leptin levels. Downstream effects of high insulin levels and insulin resistance include an association with increased visceral fat or fat around the organs. IR is also associated with high levels of blood triglycerides and it stimulates the synthesis (production) of leptin. High triglycerides will increase LR further and also prevent leptin from crossing the blood-brain barrier, another mechanism of LR.
Exposure to biotoxins in a reactive person. Some clinicians in functional medicine beat the drum of the dangers of being in a water-damaged building, and for good reason. One of the consequences of this exposure for a person who is susceptible to inflammatory processes occurring and who experiences immune system reactivity is that LR may occur. Further adiponectin levels may be significantly diminished. Think of leptin and adiponectin as yin and yang, which are both produced by fat cells. For optimal fat metabolism, you want leptin low and adiponectin high. When leptin is high, the body cannot mobilize fat stores and instead turns to protein as an energy source, and this is bad. When LR is present with inflammation, one gains weight, can't or doesn't want to exercise, and when they do, they become very tired and sore in the days after without getting any of the weight reduction benefits of exercise and instead breaking down muscle.
Signs and Symptoms of possible LR
Someone who has LR may experience:
overeating/binge eating
feeling hungry more often
weight gain
weight gain or lack of weight loss when doing appropriate lifestyle changes
abdominal obesity/ increased waist circumference
have hypertriglyceridemia
have insulin resistance, prediabetes, or type 2 diabetes
What to do?
The good news is that LR is reversible. Lifestyle changes can help reverse LR and improve metabolism. However, consideration should be given to the possibility of biotoxin illness or CIRS (chronic inflammatory response syndrome), especially when lifestyle changes are resulting in minimal improvement in biometric measurements. A functional medicine physician can be very helpful in getting to the root cause of LR and helping to reverse it.
1 Wang Y, Carreras A, Lee S, Hakim F, Zhang SX, Nair D, Ye H, Gozal D. Chronic sleep fragmentation promotes obesity in young adult mice. Obesity (Silver Spring). 2014 Mar;22(3):758-62. doi: 10.1002/oby.20616. Epub 2013 Oct 16. PMID: 24039209; PMCID: PMC3947647.
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