Acute exposure to long-chain fatty acids impairs antilipolysis in human adipose tissue

Acute exposure to long-chain fatty acids impairs α2-adrenergic receptor-mediated antilipolysis in human adipose tissue

Abstract:  The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 µmol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic {alpha}2-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an {alpha}-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the {alpha}2-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the {alpha}2-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress {alpha}2-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis. 
This article seemed to be a feather in the cap of high fat diets -- a high fat meal increases adipose tissue lipolysis!  Good, right?  Not necessarily.  Unless the freed fatty acids are subsequently "burnt" through oxidation, this leads to elevated NEFA/FFA which is not a good thing.    
The major impact of our study is to show that an acute high fat intake alters the protective function of {alpha}2-ARs against increased lipolysis in obese subjects.
Adipose tissue apparently is involved in basal insulin levels, and based on this and other studies, it is reasonable to conclude that the function of this elevated insulin is to inhibit the release of free fatty acids into the bloodstream.   The theory section in just about every LC book out there seizes on this facet of insulin's action to imply that insulin "locks" fats away in the fat cells so you can't burn it.  This is simply incorrect.  As I've posted on before, the FA/TAG cycle occurs constantly and fatty acids in our fat stores turn over continually.  Thus insulin's action here is to regulate that cycle, thus regulating the combined circulating levels of energy substrates (glucose + FFA's).   

IMO, the LC Community's boasting of lower fasting triglycerides may be premature celebration.  NEFA/FFA levels seem to be the more metabolically active form of circulating lipid that interferes with receptor signalling.  If one is insulin resistant, the most obvious and prevalent benchmark is elevated BG.  But if one controls their BG's with a very high fat low carb diet, this may elevate NEFA's, perpetuating the IR.