Leptin, Osteoarthritis & Rheumatoid Arthritis
Leptin is more than just a hormone that regulates weight & metabolism. It is also a hormone involved in inflammation and autoimmunity.
Leptin & Osteoarthritis
Leptin increases nitric oxide in joint cartilage. Nitric oxide is pro-inflammatory, leading to the death of cartilage cells.
Leptin increases metalloproteinases which degrade joints.
Leptin increases the recruitment of immune cells to inflamed joints.
Bottomline, more leptin means more joint inflammation and more degradation of cartilage.
Leptin & Rheumatoid Arthritis
Possible correlation between leptin levels and how aggressive RA is.
Correlation between leptin levels and duration of RA.
Leptin prevents the activation and proliferation of T regulatory cells that keep the immune system in check.
Bottomline, more leptin may mean more severe RA with longer flares and impaired immune activity to keep the immune system in check from attacking your joints. Also, the biologics that are primarily used to treat RA do not affect leptin levels.
Assessing & Addressing High Leptin
This information suggests that we view rheumatology through a broader lens. Instead of just focusing on what is happening in the joint space, we need to look at hormones, metabolism, and nutrition. This integrative view is common sense for many of us, but it is exciting to see the research supporting this idea.
Now, for the most part, the research only looks at leptin in obesity. So an erroneous conclusion would be to believe that leptin-arthritis connection only applies if you are obese. This is wrong for many reasons. First, obesity is defined by your body mass index, a calculation based on your weight and height. It factors in no physiology and therefore has very little meaning (other than to make people feel bad about themselves). BMI tells us nothing about your leptin levels. I have seen people with high BMI have a normal leptin level and I have seen people with a normal BMI have a high leptin level. Obviously, there is more to leptin levels than just BMI or even body fat.
So regardless on your BMI, the first step is to evaluate your fasting leptin levels through a simple blood test. More research is needed to understand optimal leptin levels, but as of now, we are aiming for less than 12 ng/mL.
Once you have established that you have elevated leptin, the next step is to lower it. There are many factors influencing leptin levels that may need to be addressed:
inflammation
glucose
insulin
cortisol
estrogen
increased fat mass
overeating
The simplest way to start decreasing your leptin levels is with your diet. Leptin levels rise 2 hours after a meal and stay elevated for 4-7 hours after a meal. Carbohydrate produce a stronger and longer leptin response due to insulin’s effects on leptin release. So modifying carbohydrate intake and fat intake is a great first step to lowering leptin levels.
References
Pérez-Pérez A, Sánchez-Jiménez F, Vilariño-García T, Sánchez-Margalet V. Role of Leptin in Inflammation and Vice Versa. Int J Mol Sci. 2020;21(16):E5887. doi:10.3390/ijms21165887
Tsuchiya H, Fujio K. Emerging role of leptin in joint inflammation and destruction. Immunol Med. Published online August 6, 2021:1-8. doi:10.1080/25785826.2021.1948689
Pereira S, Cline DL, Glavas MM, Covey SD, Kieffer TJ. Tissue-Specific Effects of Leptin on Glucose and Lipid Metabolism. Endocr Rev. 2021;42(1):1-28. doi:10.1210/endrev/bnaa027
Gruzdeva O, Borodkina D, Uchasova E, Dyleva Y, Barbarash O. Leptin resistance: underlying mechanisms and diagnosis. Diabetes Metab Syndr Obes. 2019;12:191-198. doi:10.2147/DMSO.S182406
Martin SS, Qasim A, Reilly MP. Leptin Resistance: A Possible Interface of Inflammation and Metabolism in Obesity-Related Cardiovascular Disease. Journal of the American College of Cardiology. 2008;52(15):1201-1210. doi:10.1016/j.jacc.2008.05.060
Seufert J. Leptin Effects on Pancreatic β-Cell Gene Expression and Function. Diabetes. 2004;53(suppl 1):S152-S158. doi:10.2337/diabetes.53.2007.S152
Agrawal R, Reno CM, Sharma S, Christensen C, Huang Y, Fisher SJ. Insulin action in the brain regulates both central and peripheral functions. American Journal of Physiology-Endocrinology and Metabolism. 2021;321(1):E156-E163. doi:10.1152/ajpendo.00642.2020