Low levels of the satiety hormone leptin have been linked with poor memory, anorexia, depression, and frequent infections. Read on to learn about the causes and symptoms of leptin deficiency and factors that increase and normalize it.
To learn more about normal leptin levels and what this hormone does in the body, read the first part of this series.
This post will focus on the dangers of high leptin. Elevated leptin levels are associated with obesity, overeating, and inflammation-related diseases, including high blood pressure, metabolic syndrome, and heart disease .
Leptin acts as a signal to the brain to inhibit food intake and enable the storage of surplus calories (in fat cells).
At the same time, it protects non-fatty tissue from fat overload. Increased leptin is associated with higher body fat mass, a larger size of individual fat cells, overeating, and excessive hunger. In rodents, it increases energy expenditure by using brown fat for energy .
The more fat is present, the more leptin is produced. This feedback loop, when functioning normally, keeps body weight in homeostasis: eating more food increases body fat, which increases leptin secretion, which decreases appetite and increases energy expenditure .
Low leptin levels have been associated with:
- Low body mass index (BMI) [9, 10]
- Cold exposure 
- Alcohol 
- Exercise [13, 14]
- Short-term fasting 
- Sleep deprivation 
- Anorexia 
Leptin deficiency can also be caused by disorders such as:
- Congenital leptin deficiency 
- Congenital and acquired lipoatrophy (localized loss of fat tissue) 
If you believe that your leptin system is dysfunctional, talk to your doctor about any underlying conditions or factors that may be at the root.
- Feeling hungry more often
- Difficulty losing weight (slower metabolism)
- High or low percentage of body fat
- Absent period (in women)
- Weak and brittle bones (osteoporosis)
- Frequent infection
These symptoms may also be associated with a different underlying condition. Again, the most important thing is to talk to your doctor for an accurate diagnosis and appropriate treatment or management plan.
Depression and anxiety are common in women with anorexia nervosa (AN), an illness associated with low leptin and increased ghrelin .
Similarly, there is an increased prevalence of depression and anxiety in normal-weight women with functional hypothalamic amenorrhea (HA), a disorder also characterized by low leptin and high ghrelin .
Leptin’s anti-anxiety effects are mediated in part by its actions in the Prefrontal cortex (PFC), the ventral tegmental area (VTA) and substantia nigra (SN) . Leptin also reduces anxiety by inhibiting orexin A in the suprachiasmatic nucleus (SCN) .
Leptin is believed to have some positive effects on cognitive function. Like BDNF, leptin facilitates synaptic plasticity in the hippocampus  and long-term potentiation (LTP) , processes that are critical for memory.
Animal models of Alzheimer’s disease have shown that chronic administration of leptin can be beneficial for the condition and improve cognitive performance, by reducing b-amyloid and Tau proteins, two hallmarks of Alzheimer’s pathology [26, 27].
Leptin is believed to restore fertility and may improve bone health in lean women .
Women with extremely low body fat, including runners and dancers, as well as women with eating disorders, are prone to develop hypothalamic amenorrhea (HA), a condition in which their menstrual periods cease, triggering serious problems such as infertility and osteoporosis .
Without leptin, menstrual periods cease, the body becomes chronically energy-deprived and women experience bone loss and an increased risk of bone fractures .
Treatment with a synthetic form of leptin can restore fertility and reduce the risk of bone fractures in this group of patients . This is believed to be one reason why during fasting or starvation, fertility declines .
It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility .
Leptin stimulates the maturation, production, activation, and function of human Natural Killer cells .
Leptin is secreted by the stomach and enters the small intestine. Once it reaches the intestines, leptin can interfere with the absorption of some nutrients. For example, it enhances butyrate , fructose  and oligopeptide uptake .
I could see this being both bad and good. By blocking the absorption of glucose and amino acids, it can help weight loss.
However, blocking glucose uptake gives a better chance for SIBO to arise or for malnutrition from not absorbing amino acids.
Leptin leads to the production of VIP, the anti-inflammatory hormone (synergistically with TGF-beta). VIP has mixed effects on weight, however. Although it blocks appetite, its net effect may be to promote obesity .
When stressed, you release leptin and the more you release, the more you eat comfort foods after .
Restful sleep in non-obese individuals (i.e. 8 – 12 hours of uninterrupted sleep) increased leptin to normal levels .
On the other hand, sleep deprivation can decrease leptin 
One of the first steps in improving anyone’s health is to make sure they’re getting enough sleep. This is a good place to start for the leptin system as well.
Estrogen increases leptin. This is usually bad, since excess estrogens have been linked to leptin resistance. However, if you are in menopause, maintaining estrogen activity might help balance your leptin levels. If you are concerned about your estrogen levels, work with a physician to make sure your hormones are balanced 
Leptin increases 4 – 6 hours after meals in response to insulin secretion. Check your insulin and glucose levels to make sure they are in the normal range. If you are at risk of disrupted insulin regulation, talk to your doctor about potential solutions .
Alcohol decreases leptin more compared to other calories .
Lectins are proteins that bind to sugar molecules. Leptin receptors have sugar molecules that can bind to lectins, such as ConA (in legumes) and WGA (in wheat). If the sugar molecules on leptin receptors are bound (or removed), then the receptors are blocked. If this mechanism translates to the human body, then lectins may disrupt the leptin signaling system, but this has not been investigated in clinical studies .