Subcutaneous fat cell lipolysis independent contributor to variations in plasma lipids
Subcutaneous Adipocyte Lipolysis Contributes to Circulating Lipid Levels
Circulating cholesterol and triglyceride levels are important independent risk factors for development of atherosclerotic cardiovascular disease [1,2]. As fatty acids have a role in dyslipidemia [3,4], one can think that fat cell lipolysis resulting in free fatty acids (FFAs) in the circulation, may affect the levels of cholesterol and triglycerides. For example, high FFA levels may increase the hepatic production of LDL-c, which in turn may reduce HDL-c levels by increasing transfer of triglycerides to HDL leading to hydrolysis and thereby the formation of remnant cholesterol.
The release and storage of adipose FFAs equals the turnover of measurable fat cell triglycerides [5,6]. It has been shown that forms of dyslipidemia were linked to altered triglyceride turnover and that this was proportional to subcutaneous adipocyte lipolysis activity [7-9]. Therefore, this suggest that fat cell lipolysis may affect circulating lipid levels. In humans, catecholamines and natriuretic peptides have prolipolytic activity, whereas insulin is the major hormone with antilipolytic activity.
A large study including >1000 individuals was conducted to investigate the relationship between different effectors of adipocyte lipolysis and circulating lipid levels.
- Correlations between various circulating lipids levels and lipolysis were significant, but weak (r2<0.05). However, basal lipolysis was significantly negatively and strongly correlated with HDL-c and positively and strongly with plasma triglycerides. In contrast, insulin sensitivity was positively correlated with HDL-c and negatively with triglycerides.
- The relationships between basal lipolysis with HDL-c or triglycerides were stronger in nonobese individuals (HDL-c nonobese r=-0.27, P<0.0001, obese r=-0.10, P=0.012 and triglycerides nonobese r=0.27, P<0.0001, obese r=0.12, P=0.0035). Insulin sensitivity vs HDL-c or triglyceride were equally strong in obese and nonobese individuals.
- Removing type 2 diabetes patients and individuals on antihyperlipidemic treatment from the analyses generated similar results. Similarly, there was no sex interaction in the relationship between basal lipolysis or insulin sensitivity and HDL-c or triglycerides.
- The relationships were still highly significant after correction for intrinsic/extrinsic cofactors known to influence circulating lipid levels (cofactors: sex, age, BMI, waist circumference, waist-to-hip ratio, nicotine use, treatment of type 2 diabetes, hypertension or hyperlipidemia and fat cell size).
- Combining factors revealed an adjusted r2 of 0.14 between insulin sensitivity and basal lipolysis together and both triglycerides and HDL-c (both P<0.0001). Combining all cofactors and correlate this, r2 values were 0.28 (HDL-c) and 0.17 (triglycerides, both P<0.0001). Pooling all cofactors and insulin sensitivity and basal lipolysis, r2 for HDL-c was 0.36 and for triglycerides was 0.29 (both P<0.0001).
In this study, resistance to the antilipolytic effect of insulin and a high rate of basal lipolysis are associated with low HDL-c and high triglyceride levels. This was independent of classical risk factors influencing plasma lipids. Moreover, antilipolytic insulin sensitivity and basal lipolytic activity together explained 14% of variations in plasma triglycerides or HDL-c, thereby suggesting clinical importance for dyslipidemia.