Energy expenditure, sex, and endogenous fuel availability in humans

Abstract

IntroductionApproximately 50% of postabsorptive energy needs in humans are supplied from the oxidation of fatty acids. The major source of this lipid fuel is circulating FFAs that are released from lipolysis of adipose tissue triglyceride. Maintaining normal FFA availability is of considerable importance in human health (1), because high FFA concentrations are associated with a number of cardiovascular risk factors (2) and a predisposition to type 2 diabetes mellitus (3). Experimentally increasing FFA concentrations in normal humans can induce insulin resistance (4), disordered lipoprotein metabolism (5), altered vascular reactivity (6), and abnormal insulin secretion (7).At rest, an average adult with 15 kg of body fat (>50 moles of fatty acids) releases less than 0.4 mmol/min into the circulation to provide energy for fat-free tissue. This is in striking contrast to glucose fuel, where hepatic glycogen stores are approximately 370 mmol and glucose is released at rates of approximately 0.8 mmol/min (8). Understanding the regulation of this relatively massive adipose tissue fuel depot is important given the prevalence of obesity is increasing rapidly in many Western societies.The factors that regulate changes in FFA release in response to changing lipid fuel needs are relatively well described. The insulin secretion stimulated by carbohydrate ingestion markedly inhibits FFA release, thereby suppressing FFA concentrations and fatty acid oxidation by 80-90% (9). In contrast, carbohydrate deprivation or fasting reduces insulin secretion, which enhances adipose tissue FFA release, allowing FFA concentrations to increase by approximately 300% to facilitate greater fat oxidation. Exercise, the most potent physiological stimulus to fat oxidation, can increase FFA release by more than 300% (10), primarily through increased catecholamine stimulation of adipose β-adrenergic receptors. This relatively good understanding of the short-term regulators of FFA release is not mirrored by an equal appreciation of the factors that influence average resting FFA availability.Understanding the normal interaction between adipose tissue fuel release rates and fat-free mass (FFM) fuel use rates is important for understanding the effects of body fat on health. The approach to comparing fuel release rates between groups with different weights and/or different body composition can influence how the information is interpreted, however. For example, there has been controversy regarding whether obesity causes higher FFA concentrations because of greater release or lesser clearance of FFA from the circulation. Obese adults have FFA release rates similar to lean adults, relative to body weight or body fat (11, 12), Adipose tissue lipolysis supplies circulating FFAs, which largely meet lipid fuel needs; however, excess FFAs, can contribute to the adverse health consequences of obesity. Because "normal" FFA release has not been well defined, average (mean of 4 days) basal FFA release and its potential regulation factors were measured in 50 lean a...

The effect of exercise on regional adipose tissue and splanchnic lipid metabolism in overweight Type 2 diabetic subjects

“…From this perspective, therefore, insulin resistance does not result in enhanced lipolysis. Recently it has been proposed that resting whole-body fatty acid mobilisation correlates better to resting energy expenditure than to lean body mass or fat mass [32]. The resting energy expenditure was not increased in the present subjects, while their total fat mass was about three-fold larger than that of the subjects studied previously [10,17].…”

Pioglitazone increases non-esterified fatty acid clearance in upper body obesity

“…Oleate clearance (l/min) was calculated by dividing oleate R d (μmol/min) by oleate concentration (μmol/l). Because the groups were well matched in terms of resting energy expenditure (REE) and fat-free mass (FFM) the oleate flux data are presented as μmol/min rather than dividing by units of weight or body composition [7]. Matching for relevant variables is preferable to using numerator/denominator approaches to present NEFA flux data because it prevents drawing spurious conclusions [32]; NEFA flux is most strongly predicted by REE [7].…”

“…Because the groups were well matched in terms of resting energy expenditure (REE) and fat-free mass (FFM) the oleate flux data are presented as μmol/min rather than dividing by units of weight or body composition [7]. Matching for relevant variables is preferable to using numerator/denominator approaches to present NEFA flux data because it prevents drawing spurious conclusions [32]; NEFA flux is most strongly predicted by REE [7]. Substrate oxidation was assessed using CO 2 production relative to O 2 consumption rates and urinary nitrogen excretion [33].…”

“…This is manifested by impaired glucose disposal and increased plasma NEFA concentrations. Plasma NEFA concentrations are largely determined by effective adipose tissue lipolysis, as assessed by measurements of NEFA release [6], but are also regulated by NEFA clearance [7,8]. Lipolysis is abnormally increased under both basal [3] and insulin-suppressed conditions [3,9] in upper body obesity and type 2 diabetes [4,5].…”

“…Lipolysis is abnormally increased under both basal [3] and insulin-suppressed conditions [3,9] in upper body obesity and type 2 diabetes [4,5]. The resultant higher NEFA concentrations [7] are thought to contribute to insulin resistance at the level of muscle [10,11] and liver [12], to hypertriglyceridaemia [13] and to abnormal vascular function [14]. The ability of insulin to suppress plasma NEFA concentrations following meal ingestion is thought to play an important role in peripheral glucose disposal [10] and suppression of hepatic glucose release [12].…”