Oscillations of Fatty Acid and Glycerol Release From Human Subcutaneous Adipose Tissue In Vivo

Abstract

We sought evidence for pulsatility of lipolysis in human subcutaneous adipose tissue in vivo. Arterialized and adipose tissue venous blood samples were drawn at 2-min intervals from nine healthy subjects. This procedure was repeated during hyperinsulinemic-euglycemic clamp to remove insulin pulsatility. We found evidence for pulsatile release of both nonesterified fatty acids (NEFAs) (seven of nine subjects) and glycerol (five of six subjects) with a period of ϳ12-14 min. This pulsatility was maintained even during the hyperinsulinemic clamp. Checks were made for spurious pulse detection, including the creation of "mock" venoarterialized differences by subtracting one subject's arterialized concentrations from another's venous; the peaks detected were less consistent in character than with real data (peak width, P ‫؍‬ 0.006; peak interval, P < 0.004). Significant cross-correlations between NEFA and glycerol release also provided evidence of a real effect. Arterialized norepinephrine concentrations were also pulsatile, but the period did not match that of NEFA and glycerol release. Insulin concentrations were pulsatile with a typical period of 12 min, but this was not significantly cross-correlated with lipolysis. We conclude that release from adipose tissue of the products of lipolysis is pulsatile in humans. Diabetes 54:1297-1303, 2005 I t is increasingly recognized that metabolic processes do not operate at steady rates. Oscillations in glycolytic flux, synchronized across cells, have long been recognized (1). Pulsatile secretion of hormones is also well established, and for insulin, for example, there is a clear oscillatory pattern with a characteristic period of 12-13 min observable in systemic plasma (2,3). Among the metabolic processes regulated by insulin is adipose tissue lipolysis. Recently, rapid oscillations in lipolysis have been observed in omental adipose tissue in dogs (4). These oscillations appeared to be independent of insulin, however, and were partially blocked by propranolol. More recent work in dogs has shown that oscillations of lipolysis, detected in systemic plasma nonesterified fatty acid (NEFA) concentrations, are superimposed on a steady background level of NEFA, and only the oscillatory component is blocked by specific blockade of the ␤3-adrenoceptor, which is responsible for lipolysis in dogs (5).In humans, adipose tissue lipolysis, as measured by microdialysis of interstitial glycerol, is not affected by propranolol after an overnight fast. (6). This seems surprising but might be understandable if ␤-adrenergic activation were responsible for only a small component of lipolysis; rapid oscillations might be lost with the limited time resolution of microdialysis. If pulsatile lipolysis were detectable in humans, it might considerably alter our view of NEFA release and its interaction with insulin action and glucose metabolism.Therefore, we have sought evidence for pulsatility of lipolysis in human adipose tissue. The subcutaneous upper-body adipose tissue makes the largest contributio...

Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport

“…Leptin secretion falls in early starvation (23), and there is evidence for pulsatile secretion of adiponectin and leptin (16). Pulsatile release of other hormones such as insulin and glucagon (18,25) and of products of lipolysis from adipose tissue in vivo (21), with periods of 10 -15 min, have also been reported. The pulsatile release of an adipokine would compromise the steady-state assumption necessary for our calculation of the secretion rate.…”

Advances in adipose tissue metabolism

“…97,98 Release from AT of the products of lipolysis is pulsatile in dogs 99 and in humans. 100 In vivo studies based on the use of tracer methodology have clearly shown that lipolytic activity is greater in upper-body subcutaneous than in leg AT (per kg of fat) in lean and obese men and women.…”

Stable isotope-labeled tracers for the investigation of fatty acid and triglyceride metabolism in humansin vivo

“…Furthermore, differences in tissue perfusion and possibly also in FFA extraction and/or uptake, e.g., between individual skeletal muscles [58,59], likely lead to disproportionate distribution of total FFA flux amongst fat-free tissues or different adipose tissue regions, and therefore further confound the interpretation of ratios. It is also important to note that, probably due to the pulsatile/oscillatory nature of adipose tissue lipolysis [60,61], the intra-individual day-to-day variability of plasma FFA turnover rates is considerable, ∼15-30% [62-64]. Therefore, careful attention to details and standardization of the experimental conditions (prior diet and physical activity, fasting duration, sample timing, etc.)…”