Category: Health Tips

The Link Between Excess Fat & Inflammation

As Attune Health’s in-house nutritionist, a common conversation I have with many people is about the risks associated with having excess fat. First of all, it is important to note that our bodies need fat; they possess a number of functions including the production of hormones, temperature regulation, vitamin reabsorption, and protection. Typically, for men you would want to be between 13 and 20 percent body fat, while women would want to be between 17 and 28 percent.

The issue with fat comes when there is an excess amount of it. When we accumulate extra calories as a result of overconsumption or physical inactivity, that excess energy is stored as fat, otherwise known as adipose tissue. Adipose tissue plays a large role in inflammation and immunity, so this is an important topic to talk about.




Adipose tissue has traditionally been defined as connective tissue that stores excess calories. Subcutaneous adipose tissue, which is typically what we consider when we think about body fat, is is stored under the skin. Adipose tissue can also be stored around our organs in the form of visceral adipose tissue.




Excess fat is typically associated with metabolic syndrome, a collection of conditions that includes high blood pressure (hypertension), high blood sugar (hyperglycemia), excess body fat around the waist, and abnormal cholesterol or triglyceride levels. This condition can increase your risk of heart disease, stroke, and diabetes.

If excess body fat accumulates to the extent that someone’s BMI measures above 30, that individual is considered to be obese. The most troublesome variation is central (abdominal) obesity, which is defined as an excess amount of body fat around the waist. This should make sense intuitively; think about it – your core is where you store all of your organs. If that is where you are storing fat, it is going to put stress on your body.

Additionally, obesity, specifically with excess visceral adiposity, is strongly associated with insulin resistance (a common precursor to diabetes), hypertension, and dyslipidemia, or an abnormal amount of fats – triglycerides, cholesterol, and/or fat phospholipids – in the blood. These, in turn, contribute to a high rate of morality and morbidity. Accumulating evidence indicates that a state of chronic inflammation has a vital role in the development of obesity-related metabolic dysfunction [1,2].




In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines, as well as immune and metabolic homeostasis. Adipokines are cytokines, or cell-signaling proteins, that are specifically released by adipose tissue. As excess fat accumulates and adipose tissue expands during the development of obesity, this balance of pro- and anti-inflammatory adipokines shifts in favor of inflammation.

This balance is influenced by a number of different factors, including:

  • nutritional/metabolic status
  • the presence of infection or systemic inflammation
  • oxidative stress
  • smoking status
  • age
  • sex [3-9]

The pro-inflammatory status of adipose tissue contributes to a chronic state of inflammation and metabolic disorders associated with obesity.

The most well-known pro-inflammatory adipokine is leptin, and it increases in proportion to the amount of adipose tissue present. Leptin can directly enhance the production of several pro-inflammatory factors such as Interleukin-6 (IL-6), which can help predict the chances of developing Type II diabetes [10-11]. Moreover, leptin levels are positively correlated with the severity of different diseases, including:

  • Osteoarthritis
  • Multiple Sclerosis
  • Nonalcoholic Fatty Liver Disease
  • Hepatic Fibrosis
  • Renal Disease
  • Atherosclerosis
  • Thrombosis [12-20]




One common way to reduce the size of fat cells is calorie restriction. By doing this, pro-inflammatory adipokines decline and anti-inflammatory adipokines increase, promoting an anti-inflammatory state. There is a downside, however: this effect is also associated with a suppression in immune system function. Therefore, overall, caloric restriction induces a reduction in inflammation, but at the cost of a decrease in immunity as well.




To summarize, excess fat promotes inflammation due to pro-inflammatory adipokines such as leptin, and therefore it is crucial to achieve and maintain a healthy weight. In doing so, your body will be producing more anti-inflammatory adipokines and promote immune and metabolic homeostasis.

Weight loss through a healthy diet and exercise are the best methods of sustaining a healthy weight. Creating lifelong habits is the best way to ensure long-term success.




  1. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444(7121):860-7 doi: 10.1038/nature05485[published Online First: Epub Date]|.
  2. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006;116(7):1793-801 doi: 10.1172/JCI29069[published Online First: Epub Date]|.
  3. Mancuso P, Huffnagle GB, Olszewski MA, Phipps J, Peters-Golden M. Leptin corrects host defense defects after acute starvation in murine pneumococcal pneumonia. Am J Respir Crit Care Med 2006;173(2):212-8 doi: 10.1164/rccm.200506-909OC[published Online First: Epub Date]|.
  4. Ahima RS, Prabakaran D, Mantzoros C, et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996;382(6588):250-2 doi: 10.1038/382250a0[published Online First: Epub Date]|.
  5. Sull JW, Kim HJ, Yun JE, Park EJ, Kim G, Jee SH. Serum adiponectin is associated with smoking status in healthy Korean men. Endocr J 2009;56(1):73-8
  6. Isidori AM, Strollo F, More M, et al. Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights. J Clin Endocrinol Metab 2000;85(5):1954-62 doi: 10.1210/jcem.85.5.6572[published Online First: Epub Date]|.
  7. Somech R, Reif S, Golander A, Spirer Z. Leptin and C-reactive protein levels correlate during minor infection in children. Isr Med Assoc J 2007;9(2):76-8
  8. Mancuso P, Gottschalk A, Phare SM, Peters-Golden M, Lukacs NW, Huffnagle GB. Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia. J Immunol 2002;168(8):4018-24
  9. Nakanishi S, Yamane K, Kamei N, Nojima H, Okubo M, Kohno N. A protective effect of adiponectin against oxidative stress in Japanese Americans: the association between adiponectin or leptin and urinary isoprostane. Metabolism 2005;54(2):194-9 doi: 10.1016/j.metabol.2004.08.012[published Online First: Epub Date]|.
  10. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999;282(22):2131-5
  11. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001;286(3):327-34
  12. Karvonen-Gutierrez CA, Harlow SD, Mancuso P, Jacobson J, Mendes de Leon CF, Nan B. Association of leptin levels with radiographic knee osteoarthritis among a cohort of midlife women. Arthritis Care Res (Hoboken) 2013;65(6):936-44 doi: 10.1002/acr.21922[published Online First: Epub Date]|.
  13. Karvonen-Gutierrez CA, Harlow SD, Jacobson J, Mancuso P, Jiang Y. The relationship between longitudinal serum leptin measures and measures of magnetic resonance imaging-assessed knee joint damage in a population of mid-life women. Ann Rheum Dis 2014;73(5):883-9 doi: 10.1136/annrheumdis-2012-202685[published Online First: Epub Date]|.
  14. Dattaroy D, Pourhoseini S, Das S, et al. Micro-RNA 21 inhibition of SMAD7 enhances fibrogenesis via leptin-mediated NADPH oxidase in experimental and human nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2015;308(4):G298-312 doi: 10.1152/ajpgi.00346.2014[published Online First: Epub Date]|.
  15. Bodary PF, Westrick RJ, Wickenheiser KJ, Shen Y, Eitzman DT. Effect of leptin on arterial thrombosis following vascular injury in mice. JAMA 2002;287(13):1706-9
  16. Lim CC, Teo BW, Tai ES, et al. Elevated serum leptin, adiponectin and leptin to adiponectin ratio is associated with chronic kidney disease in Asian adults. PLoS One 2015;10(3):e0122009 doi: 10.1371/journal.pone.0122009[published Online First: Epub Date]|.
  17. Hasan-Ali H, Abd El-Mottaleb NA, Hamed HB, Abd-Elsayed A. Serum adiponectin and leptin as predictors of the presence and degree of coronary atherosclerosis. Coron Artery Dis 2011;22(4):264-9 doi: 10.1097/MCA.0b013e3283452431[published Online First: Epub Date]|.
  18. Shamsuzzaman AS, Winnicki M, Wolk R, et al. Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 2004;109(18):2181-5 doi: 10.1161/01.CIR.0000127960.28627.75[published Online First: Epub Date]|.
  19. Petersen KF, Oral EA, Dufour S, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest 2002;109(10):1345-50 doi: 10.1172/JCI15001[published Online First: Epub Date]|.
  20. Cochran E, Young JR, Sebring N, DePaoli A, Oral EA, Gorden P. Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the Rabson-Mendenhall syndrome. J Clin Endocrinol Metab 2004;89(4):1548-54 doi: 10.1210/jc.2003-031952[published Online First: Epub Date]|.