The importance of leptin in managing patients with dysglycemia & metabolic syndrome

The importance of leptin in managing patients with dysglycemia & metabolic syndrome

Kevin K. Bodling

Nearly one-fourth of all Americans age 20 or older are obese, meaning that they are 30 or more pounds over their ideal weight. Obesity is linked to five of the 10 leading causes of death in the US, including diabetes. Nationwide, costs of obesity are estimated at nearly $100 billion. Over the past several years there have been numerous research papers correlating leptin and obesity. However, few people, including health care professionals, realize the importance of leptin in regulating blood sugar in the body and why it is important to test for leptin when treating patients that have blood sugar regulation disorders such as type 2 diabetes and metabolic syndrome.

Abdominal fat stores are really the key in the development of type 2 diabetes and CVD (cardiovascular disease), two of the major symptoms of metabolic syndrome. In the US, the prevalence of metabolic syndrome is 6.7% for 20- to 30-year-olds but rises to 43% between the ages of 60 and 70. In medicine, it is common practice to run tests such as fasting glucose, insulin, or hemoglobin A1c to assess these conditions, but serum leptin may prove to be a powerful tool in the early detection of metabolic syndrome and serve as a guide in helping individuals at risk of developing this condition to transition their metabolism from a sugar-burning metabolism to a fat-burning metabolism. By increasing consumption and supplementation of healthy fats like olive oil and fish oil, L-carnitine, and CLA, restricting the consumption of simple and refined carbohydrates, and exercising, these individuals will actually burn fat and subsequently reduce the burden on the pancreas, liver, and other organs.

Leptin is a 16-kDa protein hormone produced by white adipose tissue. Smaller amounts of leptin are also secreted by cells in the epithelium of the stomach, brown adipose tissue, placenta (syncytiotrophoblasts), ovaries, skeletal muscle, stomach (lower part of fundic glands), mammary epithelial cells, bone marrow, pituitary and liver. Prior to leptin’s discovery, adipose tissue was simply viewed as an energy storage reserve. After it was discovered that adipocytes produced hormones like leptin, fat became an endocrine organ like the ovaries, thyroid, pancreas, and pituitary, influencing the rest of the body, especially the brain. Leptin tells the brain what to do about life’s two main biological goals: eating and reproduction.

One of the main roles of leptin is to help control appetite. When it was first discovered, it was found that humans and mice with defects in the gene that codes for leptin would become morbidly obese due to lack of CNS stimulation by leptin, which would normally cause suppression of appetite and help control energy expenditure. When these obese mice were given exogenous leptin, they would lose weight. Ongoing research indicates that leptin not only plays an important role in the body’s response to food deprivation but is also involved in a diverse array of physiological functions including angiogenesis, hematopoiesis, immunity, bone formation, sexual development, reproduction, and blood sugar regulation. Studies have shown that humans and mice with genetic absence of leptin do not complete puberty, and increased leptin levels lead to early puberty. Leptin levels also affect fertility in females and the development of a normal pregnancy via excretion of leptin by the placenta in the second and third trimesters. Other studies show that leptin also plays a profound role in inflammation, cardiovascular disease, diabetes, osteoporosis, and all diseases of aging, and perhaps aging itself. There is also evidence that leptin plays a role in hyperemesis gravidarum (severe morning sickness), polycystic ovary syndrome, and fetal lung maturation.

In regards to blood sugar regulation and metabolism, insulin and leptin work synergistically to control the quality and rate of one’s metabolism through the nervous system control. Insulin works mostly at the individual cellular level, signaling the cell whether to burn or store fat and whether to utilize that energy for maintenance and repair or reproduction. Leptin then communicates with the brain via the hypothalamus about how much energy (fat) the body has stored, and whether it needs more, should burn some, and whether it is an advantageous time for the body to reproduce. The proposed reference ranges for serum leptin based on current research are:

* Adult Males: 1.2-9.5 ng/mL

* Adult Females: 4.1-25.0 ng/mL

Increasing leptin levels in the blood correlate with increasing body fat. Therefore, obese individuals have the highest levels of leptin, suggesting that these individuals are insensitive to leptin (“leptin resistant”) as opposed to suffering from leptin deficiency. Leptin resistance is caused by the same general mechanism as “insulin resistance.” As the hormone concentration level in the blood becomes elevated, the corresponding receptor cells become resistant to the hormone over time, thereby requiring an even higher concentration of hormone to produce the desired effect. In the case of leptin, as fat storage increases, more leptin is produced, which over time causes the receptor cells in the hypothalamus and other target tissues to become “resistant” to it. The effect is a reduction in the feeling of satiation after meals, similar to the effect caused by low leptin levels. Therefore, these individuals feel like they are hungry all the time so they eat more and gain more body fat perpetuating this cycle. One proposed mechanism of leptin resistance is the desensitization or down-regulation of the signaling form of the leptin receptor (Ob/Rb) and the induction of a protein called SOCS3, which inhibits leptin signaling. Both Ob-Rb and SOCS3 can be detected in blood monocytes.

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In lean individuals leptin, along with adiponectin, is pivotal in preventing ectopic lipid accumulation, which is the accumulation of fat outside the usual fat stores (i.e., in places other than adipose tissue). A drop in adiponectin coupled with leptin resistance leads to ectopic lipid accumulation in various tissues and organs, especially in the abdomen. When this occurs in muscle, it leads to insulin insensitivity (a relative inability of insulin to facilitate the disposal of glucose in tissues). Insulin insensitivity is the first step towards the development of both type 2 diabetes and heart disease. Lipid accumulation in pancreatic beta cells, the site of insulin production, contributes to the development of type 2 diabetes and in cardiomyocytes contributes to cardiovascular disease. Furthermore, in obesity the release of growth hormone declines, exacerbating the decline normally seen with aging and perpetuating obesity through the loss of the hormone’s muscle-building and fat-burning effects.

Therefore, the key to interrupting ectopic lipid accumulation and the resulting dysglycemia and metabolic syndrome is to re-sensitize leptin receptors and lower the leptin levels in the blood by transitioning the metabolism to a fat-burning metabolism via omega-3 fatty acids, CLA, L-carnitine, lowering simple and eliminating refined carbohydrates, and exercising in adequate amounts.

Since its discovery in 1994, leptin has radically changed the way science looks at fat, nutrition, and metabolism. Now it’s time for medicine to catch up and start looking at leptin when assessing these patients and stop promoting a “low fat” diet to combat obesity and blood sugar dysregulation.

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by Kevin K. Bodling, DC, DACBN

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