When it comes to maintaining weight and energy expenditure, the thyroid and leptin are the perfect pair.
As essential elements in the HPA-T Axis, the thyroid hormones help regulate how quickly cells burn fuel for energy. This control over metabolism affects body weight and energy expenditure. 
Leptin, a hormone made by fat cells, regulates appetite, metabolic efficiency, and body weight/composition, [6, 7] and has a strong influence on the HPA-T Axis. 
Leptin travels through the bloodstream to its receptors in the “appetite center” of the hypothalamus in the brain. Leptin tells the hypothalamus that the body has had enough to eat, i.e., it creates satiety. [7, 15, 18] When leptin and the thyroid are functioning normally, leptin encourages the hypothalamus to upregulate the HPA-T Axis, ensuring efficient metabolism by restricting food intake and enhancing energy expenditure. [2, 6, 12]
Weight, Thyroid, and Leptin Resistance
Weight and thyroid issues including low thyroid levels affect metabolism and body composition. [10, 14] In combination with inflammatory signaling, weight and thyroid imbalances can lead to leptin resistance and weight gain. [4, 8, 13]
Too much leptin produced by excess fat cells can cause some leptin receptors to shut down. This is leptin resistance. 
The hypothalamus doesn’t get the “I’m full” message of satiety from leptin, so the brain thinks it does not have enough nutrients, and enters a starvation mode.
The hypothalamus then increases appetite and decreases energy expenditure, slowing down the metabolic rate and modifying neuroendocrine function to favor survival.
Thus, as we see in many cases today, the body is told to keep eating food while the thyroid slows metabolism, conserving body resources and leading to weight gain.
Weight and Leptin Resistance
People with elevations in weight have high leptin levels, indicating leptin resistance. 
Weight and leptin resistance impair thyroid function, as there is an inverse relationship between thyroid hormone T3 and leptin serum concentrations. 
Increases in weight enhance resistance to leptin,  and overfeeding contributes to leptin resistance. Thus, a vicious cycle is perpetuated in which the body is told to consume more and more food, and becomes more resistant to leptin. Meanwhile, the HPA-T Axis and other systems become increasingly imbalanced. 
Leptin resistance can also lead to poor blood sugar management in people who are overweight. 
Leptin Sensitivity and Rebalancing HPA-T Axis Function
The only solution is to reverse leptin resistance.
Regaining leptin sensitivity will cause a boost to the thyroid, helping to rebalance the HPA-T Axis.
Leptin resistance can be reversed by losing weight, especially in those who are overweight.  Lifestyle interventions including diet and exercise are particularly beneficial for weight loss and regaining leptin sensitivity.
Calorie restriction can improve responsiveness to leptin,  and insulin-sparing diets with foods low on the glycemic index and low in trans fats may contribute to weight loss.
Additionally, avoiding fructose (especially high fructose corn syrup) can be helpful, as excess fructose consumption can contribute to leptin resistance. 
Regular physical activity can be significantly beneficial for improving lipid profiles (lowering triglycerides, raising HDL cholesterol) and cardiorespiratory fitness, lowering insulin levels, and supporting a healthy weight. [5, 11] Exercise has also been shown to make significant improvements in blood sugar management, blood pressure, and metabolism— conditions associated with elevated weight and leptin resistance. 
Ensuring around eight hours of sleep each night is also important, as adequate sleep is necessary for maintaining leptin levels. 
HPA-T Axis, Leptin, and Quality of Life
Proper function of the HPA-T Axis and the leptin pathway is one key to maintaining a healthy weight and quality of life. Whether for promoting a healthy weight or reversing leptin resistance, monitoring the HPA-T Axis and incorporating lifestyle changes can help the body achieve optimal function.
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Clinical Support Specialist at Sanesco International, Inc.
Emily Harrill is our newest Clinical Support Specialist, and a graduate of UNC Asheville with a Bachelor of Science in Health and Wellness Promotion. Improving quality of life for others is her ultimate goal. She enjoys being a part of the team at Sanesco, exploring wellness through the HPA-T Axis and encouraging others to use holistic, integrative means to achieve balanced health. She loves participating in challenging, empowering, and fun activities – especially Olympic weightlifting and belly dance.