Leptin Deficiency & Factors that Increase Leptin

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. What is Leptin?

Leptin is a satiety hormone that promotes weight loss . It is produced by the body’s fat cells [ 1 ].

When a person eats enough food, leptin is released into the bloodstream, where it travels to the brain, signaling that they are full and that can burn calories at a normal rate [ 2 , 3 , 4 ].

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 [ 5 ]. Leptin’s Role in Weight

To recap, leptin is one of the big 4 hormones that determine weight. It is made in fat tissue, while receptors for it are dense in two important brain regions (the hypothalamus and hippocampus) [ 6 ].

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 [ 7 ].

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 [ 8 ]. Leptin Deficiency (Low Leptin)

Causes

Low leptin levels have been associated with:

Leptin deficiency can also be caused by disorders such as:

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. Symptoms

Symptoms of low leptin levels vary depending on the underlying cause. The following symptoms have been associated with low leptin [ 17 , 18 , 19 , 20 ]: 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. Leptin’s Beneficial Health Effects

1) Anxiety and Depression

Recent studies suggest that leptin may have antidepressant and anti-anxiety properties. In rat models of depression and anxiety, leptin levels are low. When given leptin, symptoms improve [ 21 ].

On the other hand, Ghrelin , the hunger hormone, causes anxiety and depression [ 21 ], which may lead to feeling ‘hangry’ (hungry and angry).

Depression and anxiety are common in women with anorexia nervosa (AN), an illness associated with low leptin and increased ghrelin [ 21 ].

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 [ 21 ].

Recently, obesity has been linked to an increased risk of depression and anxiety [ 21 ], which can result from leptin resistance. High leptin levels were associated with lower depression scores [ 21 ].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) [ 21 ]. Leptin also reduces anxiety by inhibiting orexin A in the suprachiasmatic nucleus (SCN) [ 22 ]. 2) Ketosis Leptin may help the body get into ketosis . Leptin-deficient mice do not get into ketosis well and have a defective response to the ketogenic diet (no increase in liver FGF2 1 ) [ 23 ].It might improve mitochondrial function (by increasing hsp60), which decreases insulin resistance [ 24 ]. 3) Cognitive Function Leptin is believed to have some positive effects on cognitive function. Like BDNF , leptin facilitates synaptic plasticity in the hippocampus [ 6 ] and long-term potentiation ( LTP ) [ 6 ], processes that are critical for memory.Leptin also helps spatial learning [ 6 ] and increases BDNF in the hypothalamus (VMH) [ 25 ].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 ]. 4) Female Hormones (Fertility & Bone Health) Leptin is believed to restore fertility and may improve bone health in lean women [ 28 ].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 [ 28 ].Without leptin, menstrual periods cease, the body becomes chronically energy-deprived and women experience bone loss and an increased risk of bone fractures [ 28 ].Treatment with a synthetic form of leptin can restore fertility and reduce the risk of bone fractures in this group of patients [ 28 ]. This is believed to be one reason why during fasting or starvation, fertility declines [ 28 ].Leptin helps fertility by increasing luteinizing hormone ( LH ), follicle stimulating hormone ( FSH ) and human chorionic gonadotropin ( hCG ) [ 29 , 30 ].Excess ghrelin may reduce fertility by inhibiting GnRH [ 31 ]. 5) Immunity It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility [ 32 ].The decline of leptin during fasting is one of the main mechanisms by which fasting may suppress the immune system [ 32 ]. Natural Killer Cells People […]

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