Obesity is a known risk factor for developing metabolic diseases such as non-alcoholic fatty liver disease (NAFLD)1. An increasing amount of evidence shows that obesity induced adipose tissue dysfunction and NAFLD development are closely related2. Obesity induced changes to adipokine secretion can have detrimental effects on adiponectin and adipose tissue-liver crosstalk, leptin and inflammation, and insulin sensitivity3,4. Evidence indicates that adipose tissue dysfunction and insulin resistance can impact the regulation of de novo lipogenesis and lead to NAFLD5. Since adipokines are essential for adipose tissue-liver crosstalk, the adiponectin to leptin ratio may be a potential biomarker to investigate changes in the adipokines as well as metabolic disturbances caused by obese adipose tissue6.
Research demonstrates that obesity has many detrimental effects on adipose tissue (AT), including obesity induced changes to adipokine secretion. Studies illustrate adipose tissue from obese individuals produces an increased amount of proinflammatory adipokines7,8. Whereas, levels of anti-inflammatory adipokines that promote insulin sensitivity are decreased7,9. This shift toward proinflammatory adipokines secreted by obese AT promotes a constant state of inflammation7,9. The excess inflammation can induce more changes to obese AT including:
Both the concentration and function of adiponectin are affected by obese adipose tissue. During normal adipose tissue-liver crosstalk, the liver relies on AT to secrete adequate amounts of adiponectin to stimulate β-oxidization and promote insulin sensitivity3,9. However, studies show that obese individuals have lower levels of adiponectin and, therefore, may only have a limited amount available to perform these duties3,9. In turn, the body tries to combat the decrease in adiponectin by increasing the amount of insulin secreted by pancreatic β-cells. Over time, the concentration of insulin in circulation increases which can promote the development of insulin resistance2.
Leptin concentration and function are also affected by obese adipose tissue. Research indicates that leptin secretion increases with fat mass percentage and obese individuals also have high concentrations of the adipokine4,12,13. Studies have uncovered that increases in leptin activate the adipokine’s proinflammatory effects on the body4. The leptin receptor is expressed by many immune cells such as macrophages and eosinophils4. When leptin binds to these immune cells, it promotes the generation of proinflammatory cytokines4. The secreted cytokines such as IL-6 and TNF-alpha then promote the secretion of leptin, creating a detrimental inflammation loop4. Over time, the combination of inflammation and excessive free fatty acids reduces fatty acid oxidization and promotes insulin resistance4.
Nonalcoholic fatty liver disease is now recognized as a part of metabolic syndrome, and an estimated 20-30% of adults have the disease14,15. NAFLD is characterized by excessive fat accumulation in the liver not associated with alcohol consumption14,16. Current research demonstrates that many factors contribute to the development of NAFLD including obesity induced adipose tissue dysfunction14.
Insulin resistance promoted by obesity induced adipose tissue dysfunction is a risk factor for developing NAFLD2. Studies reveal that as adipocytes grow larger to accommodate the increased demand for lipid storage, the cytoskeletons of adipocytes can become dysfunctional and impair insulin signaling7. As insulin resistance progresses in adipose tissue and throughout the body, pancreatic β-cells increase their secretion to compensate for the elevated need for insulin. The continual high demand for insulin can lead to a decline in β-cell function, health, and mass17.
Research shows that obese adipose tissue and insulin resistance can also negatively impact the regulation of de novo lipogenesis in the liver5. Insulin resistance promotes de novo lipogenesis and lipid storage in the liver by:
These occurrences cause an imbalance in both lipid and glucose metabolism. Furthermore, lipid accumulation in the liver driven by insulin resistance can cause inflammation and lead to the development of NAFLD5,18.
Both adiponectin and leptin have become key biomarkers in researching metabolic diseases such as NAFLD due to their associations with energy metabolism. Adiponectin and leptin levels have separately been associated with the risk of various metabolic diseases:
Due to variances in the concentrations of adiponectin and leptin, investigations suggest studying the adiponectin to leptin ratio may be better than measuring the adipokines alone. These variances in concentration may be linked to:
Therefore, the adiponectin to leptin ratio may be beneficial for use in metabolic disease studies investigating fasted vs. fed changes in the adipokine concentrations20. One study shows that the ratio of adipokines is a better noninvasive predictor of NAFLD in obese adolescents than when measured separately21. More research is needed, however, to verify that the adiponectin to leptin ratio is a superior biomarker of NAFLD than adiponectin or leptin alone.
Research demonstrates that adipose tissue function can be greatly impacted by obesity. Obesity induced changes to adipokine secretion can interfere with adiponectin and adipose tissue-liver crosstalk3,9. Additionally, obese adipose tissue can create an imbalance between adiponectin and leptin concentrations, which can lead to a milieu of damaging inflammation and insulin resistance2. Adipose tissue dysfunction and insulin resistance can further impair energy balance by promoting de novo lipogenesis in the liver5,18. Measuring the adiponectin to leptin ratio may be useful in researching obesity induced adipose tissue dysfunction and NAFLD development. However, more research is still needed to understand if the adiponectin to leptin ratio is a better biomarker of NAFLD than measuring each adipokine separately8,20,21.