From the Guidelines
Low leptin levels, or hypoleptinemia, indicate a state of energy deficiency in the body, which can occur due to insufficient fat stores, caloric restriction, or conditions like anorexia nervosa, and is associated with various physiological and hormonal changes that conserve energy 1.
Key Points
- Leptin is a hormone primarily produced by fat cells that helps regulate energy balance by inhibiting hunger.
- When leptin levels are low, it typically means the body has insufficient fat stores or is experiencing caloric restriction, which can trigger increased appetite, reduced energy expenditure, and hormonal changes that conserve energy.
- Low leptin levels can occur during fasting, significant weight loss, or in conditions like anorexia nervosa, and are associated with decreased thyroid function, reduced reproductive hormones, and increased stress hormones 1.
- Chronically low leptin levels may contribute to difficulty maintaining weight loss, as the body attempts to restore fat stores.
- Treatment approaches depend on the underlying cause but may include addressing any eating disorders, ensuring adequate nutrition, or in rare cases of genetic leptin deficiency, leptin replacement therapy, as supported by studies on the role of leptin in energy homeostasis and immune responses 1.
Physiological and Hormonal Changes
- Decreased thyroid function
- Reduced reproductive hormones
- Increased stress hormones
- Increased appetite
- Reduced energy expenditure
Conditions Associated with Low Leptin Levels
- Anorexia nervosa
- Significant weight loss
- Fasting
- Genetic leptin deficiency
- Energy deficiency states, such as Relative Energy Deficiency in Sport (REDs) 1
Importance of Leptin in Energy Homeostasis and Immune Responses
- Leptin plays a crucial role in regulating energy balance and immune responses, with effects on both myeloid and lymphoid cells 1.
- Leptin deficiency can lead to impaired immune function, increased susceptibility to infections, and altered inflammatory responses 1.
- Leptin replacement therapy may be beneficial in conditions associated with leptin deficiency, such as anorexia nervosa and genetic leptin deficiency, to restore energy homeostasis and immune function 1.
From the Research
Hypoleptinemia Indications
Hypoleptinemia, or low leptin levels, has been associated with various health conditions, including:
- Increased risk of cardiovascular events and mortality in patients with stable coronary artery disease 2
- Atherosclerosis risk factors, such as inflammation, obesity, diabetes mellitus, hypertension, and sleep disorders 3
- Cardiovascular diseases, including coronary artery disease, stroke, carotid artery disease, peripheral artery disease, and abdominal aortic aneurysms 4
- Type 2 diabetes mellitus, with leptin levels positively associated with the presence, severity, and poor clinical outcomes of the disease 4
- Lipodystrophy, hypothalamic amenorrhea, and congenital leptin deficiency, where leptin replacement therapy has shown improvement in metabolic and endocrine functions 5
Health Implications
Low leptin levels can have significant health implications, including:
- Increased risk of macrovascular and microvascular complications in patients with type 2 diabetes mellitus 6
- Impaired cardiac metabolism, increased cardiac inflammation, and greater fibrosis 6
- Adverse effects on multiple atherosclerotic risk factors, including inflammation, obesity, and diabetes mellitus 3
- Potential link to chronic kidney disease incidence and progression, as well as insulin resistance and micro- and macrovascular diabetic complications 4