What is Leptin?

While overweight issues may look bad on the outside, the cascade of deleterious effects they pose internally is the hidden danger most people overlook. What is it that causes these internal disturbances? Research is showing that many of the health risks associated with obesity may in fact be derived from hormones secreted from adipocytes, called adipokines. This composition will look at the pros and cons of a particularly intriguing adipokine—leptin.

Leptin is a peptide hormone secreted mostly in white adipose tissue (WAT) of humans and circulates in the blood at concentrations proportional to fatness (i.e. the fatter you are, the higher your leptin levels should be, more on this later). Leptin’s most pronounced physiological effects arise from neuromodulation of peptides in the hypothalamic-pituitary-thyroid axis (HPTA).1

Therefore, leptin has major implications on hunger signaling and is antagonistic to the gut hormone ghrelin; ghrelin works to stimulate orexigenic (hunger-inducing) neuropeptides while leptin is supposed to stimulate anorexigenic (hunger-reducing) neuropeptides. Thus, leptin’s main function in the body is normalizing calorie expenditure and calorie intake, both of which directly influence body composition.

Leptin’s Effect on Body Composition

In the case of obesity, studies have shown there appears to be a downregulation of leptin receptor activity in overweight individuals, which would explain why overweight people continue to consume excessive amounts of food despite having high levels of circulating leptin.2 Research suggests that leptin resistance is brought upon by inflammation (which is generally high in overweight individuals).

Furthermore, a study in the Journal of Biological Chemistry found that exogenous doses of leptin in rats increased insulin sensitivity, as well as improved glucose regulation via hepatic suppression of gluconeogenesis.3 Basically, having high levels of leptin makes the body more efficient at handling carbohydrates.

This finding has led to the hypothesis that leptin drug development is the “next big thing” for treatment of insulin resistance and type-2 diabetes that obese individuals are often conflicted with. Alas, obese/over-fat individuals are generally resistant to the effects of leptin so the efficacy of leptin drugs is yet to be determined in overweight populations.

The ramifications of leptin resistance are readily apparent; the correlation of leptin resistance to obesity is no coincidence. However, the good news is that leptin resistance, much like insulin resistance, is reversible with proper diet and exercise. It is intriguing, nevertheless, to see what pharmaceutical interventions are in the works to augment leptin receptors. It would be a major leap forward in the battle against obesity if such drugs become available.

How to Increase Leptin Levels

By this point you’re probably thinking, “Okay, this is all great, but how in the heck do I boost my leptin levels?” The answer is not to get fat, as some people may assume (since leptin is a hormone that comes from fat); instead, the most prudent way to boost leptin levels is actually to maintain a relatively lean body composition and make sure you’re eating plenty of fiber and omega-3 fatty acids, and getting adequate rest.

Dietary Fiber

When you eat a sufficient amount of dietary fiber, you train you gastrointestinal system to communicate signals to your brain that stimulate release of leptin (which as noted earlier, stimulates hormones that increase satiety). You should be taking at least 15% of your total carbohydrate intake from fiber; so someone eating 300g of carbs per day would aim for a minimum of 45g of fiber (which isn’t that hard to reach if you’re eating a decent amount of vegetables and whole grains).

Omega-3 Fatty Acids

Furthermore, omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) boost leptin levels by reducing inflammation in the body.4 It is suggested to consume roughly 1-2g of each EPA and DHA per day (though don’t overdo it, as taking in too many omega-3 fatty acids can have negative implications). Marine food sources are generally abundant with omega-3 fatty acids, especially fish such as salmon and tuna.

Another prudent way to take in sufficient amounts of omega-3s is to supplement with fish oil. Make sure to read the label and check for how much EPA and DHA is in each serving, as some companies cut cost by using low-quality fish oil that has minimal EPA/DHA content.

Sleep

Sleep deprivation is never a good thing, especially if you’re an active individual and looking to stay lean. Studies have repeatedly shown that even acute episodes of sleep loss can have dramatic, negative effects on appetite and insulin sensitivity.5

Moreover, sleep loss is associated with increased body mass index (BMI), higher levels of ghrelin, and lowered levels of leptin.6 Essentially, when you lose sleep, you’re losing your body’s ability to properly regulate blood glucose and your hunger signaling goes haywire—not a good combo for staying (or getting) lean.

Take-Home Points

Leptin is definitely a critical hormone/adipokine that ultimately determines how much energy you consume and expend on daily basis. The good news is that, much like those with insulin resistance, leptin resistance is reversible if you keep a proper diet and exercise regimen, and lead a healthy lifestyle (with plenty of sleep). Remember to keep your omega-3 intake sufficient and eat plenty of fiber as well. In future articles we will examine other key adipokines that have implications on body composition.

References:

  1. Hebebrand, J, Td Muller, K Holtkamp, and B Herpertz-Dahlmann. "The role of leptin in anorexia nervosa: clinical implications." Molecular Psychiatry aop.current (2003): 1409-1421. Print.
  2. Jéquier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci. 2002 Jun; 967:379-88. Review. PubMed PMID: 12079865. Cited in PMCRelated citations
  3. Liu L, Karkanias GB, Morales JC, Hawkins M, Barzilai N, Wang J, Rossetti L. Intracerebroventricular leptin regulates hepatic but not peripheral glucose fluxes. J Biol Chem. 1998 Nov 20;273(47):31160-7. PubMed PMID: 9813020.
  4. Siriwardhana, N., Kalupahana, N. S., & Moustaid-Moussa, N. (2012). Health benefits of n-3 polyunsaturated fatty acids: eicosapentaenoic acid and docosahexaenoic acid. Adv Food Nutr Res65, 211-222.
  5. Arora, T., Chen, M. Z., Cooper, A. R., Andrews, R. C., & Taheri, S. (2016). The Impact of Sleep Debt on Excess Adiposity and Insulin Sensitivity in Patients with Early Type 2 Diabetes Mellitus. Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine.
  6. Taheri, S., Lin, L., Austin, D., Young, T., & Mignot, E. (2004). Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med1(3), e62.