On the suppression of plasma nonesterified fatty acids by insulin during enhanced intravascular lipolysis in humans
ABSTRACT During the fasting state, insulin reduces nonesterified fatty acid (NEFA) appearance in the systemic circulation mostly by suppressing intracellular lipolysis in the adipose tissue. In the postprandial state, insulin may also control NEFA appearance through enhanced trapping into the adipose tissue of NEFA derived from intravascular triglyceride lipolysis. To determine the contribution of suppression of intracellular lipolysis in the modulation of plasma NEFA metabolism by insulin during enhanced intravascular triglyceride lipolysis, 10 healthy nonobese subjects underwent pancreatic clamps at fasting vs. high physiological insulin level with intravenous infusion of heparin plus Intralipid. Nicotinic acid was administered orally during the last 2 h of each 4-h clamp to inhibit intracellular lipolysis and assess insulin's effect on plasma NEFA metabolism independently of its effect on intracellular lipolysis. Stable isotope tracers of palmitate, acetate, and glycerol were used to assess plasma NEFA metabolism and total triglyceride lipolysis in each participant. The glycerol appearance rate was similar during fasting vs. high insulin level, but plasma NEFA levels were significantly lowered by insulin. Nicotinic acid significantly blunted the insulin-mediated suppression of plasma palmitate appearance and oxidation rates by approximately 60 and approximately 70%, respectively. In contrast, nicotinic acid did not affect the marked stimulation of palmitate clearance by insulin. Thus most of the insulin-mediated reduction of plasma NEFA appearance and oxidation can be explained by suppression of intracellular lipolysis during enhanced intravascular triglyceride lipolysis in healthy humans. Our results also suggest that insulin may affect plasma NEFA clearance independently of the suppression of intracellular lipolysis.
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- "In the postprandial state, insulin regulates plasma FFA concentrations by suppressing intracellular adipose tissue lipolysis (33) and by reducing FFA spillover from chylomicron triglyceride lipolysis (34,35). The rise of FFAs after OLTT in spite of the rise of plasma insulin concentration is likely to reflect the spillover of FFAs from intravascular lipolysis of triglyceride-rich lipoproteins. "
ABSTRACT: OBJECTIVES Elevated plasma free fatty acids (FFAs) are one important link between excess visceral adiposity, insulin resistance, and the development of type 2 diabetes. Effects of lifestyle interventions on FFA metabolism are poorly known. This open-label study was conducted to test the effects of a 1-year healthy eating/physical activity intervention program on plasma FFA homeostasis in 117 viscerally obese men with dyslipidemia associated with insulin resistance (waist circumference ≥90 cm; triglycerides ≥1.69 mmol/L; and/or HDL-cholesterol <1.03 mmol/L).RESEARCH DESIGN AND METHODS Body weight, body composition, and fat distribution were assessed by dual-energy X-ray absorptiometry/computed tomography. Oral loads of lipid (60 g fat/m(2) body surface area) and glucose (75 g) were measured before and after the intervention.RESULTSAfter 1 year of lifestyle intervention, visceral adiposity was reduced by -26% (95% CI -29 to -23), whereas cardiorespiratory fitness improved by +20% (95% CI +16 to +24). After 1 year, the suppression of FFAs after the glucose load improved, whereas insulin concentrations were drastically reduced. After the oral lipid load, the late increase in FFA was reduced together with reduced circulating insulin. We calculated an insulin sensitivity index to reflect the concentration of insulin needed to manage plasma FFAs after the oral lipid load, which increased after the intervention and was associated with improved glucose tolerance, independent of changes in visceral or total adiposity.CONCLUSIONSA 1-year healthy eating/physical activity intervention improved the suppression of FFAs after oral glucose and lipid load tests in viscerally obese men, possibly due to improved responsiveness to insulin. This insulin-mediated regulation of postprandial plasma FFA levels could be a link between visceral obesity and impaired glucose homeostasis.Diabetes care 05/2013; 36(10). DOI:10.2337/dc12-2353 · 8.57 Impact Factor
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ABSTRACT: An automated open resonator system designed and constructed for precision measurement of loss tangent and dielectric permittivity of low absorbing materials at 60 GHz is reported. The use of a high-Q hemispherical Fabry-Perot cavity together with highly stabilized synthesized phase-locked Gunn oscillator sources and the superheterodyne receiver enabled a loss tangent value as low as 10 μrad to be measured. The system is automated by means of a precision lock-in amplifier, a V-band Hewlett-Packard spectrum analyzer and a Hewlett-Packard Vectra computer system with analog-to-digital conversion accessories. The synthesizer allows the collection of data at very small steps over the complete Gaussian beam, and, together with a statistical fitting, the Q determination can be made very accuratelyIEEE Transactions on Microwave Theory and Techniques 01/1990; DOI:10.1109/MWSYM.1990.99777 · 2.94 Impact Factor
Conference Paper: Vertical benchmarks for CAD[Show abstract] [Hide abstract]
ABSTRACT: Vertical benchmarks are complex system designs represented at multiple levels of abstraction. More effective than component-based CAD benchmarks, vertical benchmarks enable quantitative comparison of CAD techniques within or across design flows. This work describes the notion of vertical benchmarks and presents our benchmark, which is based on a commercial DSP, by comparing two alternative design flowsDesign Automation Conference, 1999. Proceedings. 36th; 02/1999