Influence of Free Fatty Acid Concentrations and Weight Loss on Adipose Tissue Direct Free Fatty Acid Storage Rates

Author(s):  
Qingyi Jia ◽  
B Gisella Carranza Leon ◽  
Michael D Jensen

Abstract Context The factors that determine the recycling of free fatty acids (FFA) back into different adipose tissue depots via the direct storage pathway are not completely understood. Objective To assess the interactions between adipocyte factors and plasma FFA concentrations that determine regional FFA storage rates. Design We measured direct adipose tissue FFA storage rates before and after weight loss under high FFA (intravenous somatostatin and epinephrine) and low (intravenous insulin and glucose) FFA concentrations. Setting Mayo Clinic Clinical Research Unit. Patients Sixteen premenopausal women, BMI 30 - 37 kg/m 2. Intervention Comprehensive lifestyle weight loss program. Main Outcome Measure Direct FFA storage rates in upper and lower body subcutaneous fat. Results Over the entire range of FFA and under isolated conditions of elevated FFA concentrations the storage rates of FFA into upper and lower body subcutaneous fat per unit lipid were associated with concentrations, not adipocyte fatty acid storage factors. Under low FFA conditions, direct FFA storage rates were related to adipocyte CD36 content, not tissue level content of fatty acid storage factors. Weight loss did not change these relationships. Conclusions The regulation of direct FFA storage under low FFA concentration conditions appears to be at the level of the cell/adipocyte content of CD36, whereas under high FFA concentration conditions direct FFA storage at the tissue level is predicted by plasma FFA concentrations, independent of adipocyte size or fatty acid storage factors. These observations offer novel insights into how adipose tissue regulates direct FFA storage in humans.

1996 ◽  
Vol 270 (2) ◽  
pp. E259-E264 ◽  
Author(s):  
M. D. Jensen ◽  
P. E. Cryer ◽  
C. M. Johnson ◽  
M. J. Murray

Upper-body and lower-body adipocytes respond differently to physiological catecholamines in vitro. It is not known whether this is true in vivo or whether gender differences exist in the regional adipose tissue responses to epinephrine. These studies were therefore conducted to examine free fatty acid (FFA) release ([3H]palmitate) from lower-body (leg), splanchnic, and upper-body adipose tissue in normal-weight adult men (n = 8) and women (n = 7). In response to intravenous epinephrine (10 ng.kg-1.min-1), palmitate release increased (P < 0.01) in both men (168 +/- 10 to 221 +/- 15 mumol/min) and women (177 +/- 12 to 234 +/- 18 mumol/min). Basal leg palmitate release was similar in women and men (16.8 +/- 2.9 and 12.4 +/- 1.3 mumol/min, P = not significant) but doubled (P < 0.01) in response to epinephrine in men and was virtually unchanged in women. Splanchnic palmitate release increased (P < 0.05) in men (n = 6) but not in women (n = 6), whereas nonsplanchnic upper-body palmitate release increased more in women than in men. Upper-body (splanchnic and nonsplanchnic) palmitate release increased (P < 0.05) in both men and women in response to epinephrine. In summary, lower-body adipose tissue FFA release increased in response to epinephrine in men but not women, whereas upper-body palmitate release increased in both groups. These findings are consistent with some in vitro findings and suggest that catecholamine action may play a role in determining gender-based differences in body fat distribution.


1961 ◽  
Vol 201 (3) ◽  
pp. 540-546 ◽  
Author(s):  
William Benjamin ◽  
Alfred Gellhorn ◽  
Mary Wagner ◽  
Harold Kundel

Lipid metabolism and chemistry was studied in adipose tissues of the rat from the age of 38 days to 647 days. Aging process was characterized by a marked decrease in lipid synthesis from acetate, a reduction in the proportion of glucose metabolized by the pentose phosphate pathway, and a lower rate of palmitate incorporation into the mixed lipids. Oxidation of palmitic acid to CO2 and release of free fatty acid by epididymal fat was the same in young and old tissues under control conditions; when, however, glucose was absent from the medium or when epinephrine was added, there was a significantly greater rate of palmitic acid oxidation and free fatty acid release by young compared to old adipose tissue. Rate of acetate incorporation into mixed lipids by multiple adipose tissue sites was determined at different ages. Consistently greater rates of lipid biosynthesis were found in the epididymal, perirenal, mesenteric and interscapular adipose tissues than in subcutaneous fat at all ages. Rate of lipid synthesis by the interscapular fat (unlike any of the other depots) remained high at all ages studied. A greater proportion of short chain fatty acids was found in adipose tissues from young rats than in the old. This was related to fatty acid composition of rat milk.


1983 ◽  
Vol 245 (4) ◽  
pp. E332-E337 ◽  
Author(s):  
C. C. Coimbra ◽  
R. H. Migliorini

In initial exploratory experiments, bilateral, symmetrical, relatively large electrolytic lesions were produced, injuring anterior, middle, and posterior hypothalamus but respecting the midlateral region. Only lesions in the preoptic-anterior hypothalamic region and in the posterior hypothalamus were effective in blocking free fatty acid (FFA) mobilization induced by intravenous 2-deoxyglucose. Lesions in the ventromedial hypothalamus were ineffective. In subsequent experiments, suppression of plasma FFA response to the drug was observed in rats with small, globular (0.5-1.0 mm diam), bilateral lesions either in the preoptic (PO) or in the lateral hypothalamic (LH) areas. Groups of animals were then prepared in which a unilateral lesion in the PO area was combined with a contralateral lesion in the LH area. Plasma FFA response to 2-deoxyglucose in these rats was also blocked but not in rats having only unilateral lesions. The hyperglycemic response to 2-deoxyglucose was not affected in any of the experimental groups. These data suggest that a longitudinal pathway connecting PO, LH, and posterior hypothalamic areas is involved in FFA mobilization from adipose tissue in rats.


1986 ◽  
Vol 251 (6) ◽  
pp. E703-E706 ◽  
Author(s):  
C. C. Coimbra ◽  
R. H. Migliorini

Previous studies indicated that a longitudinal pathway connecting preoptic, lateral, and posterior hypothalamic areas participates in the process of free fatty acid (FFA) mobilization in the rat. In the present experiments, the presence of sensitive neurons in the preoptic area was investigated by examining the effects of topical stimulation with 2-deoxyglucose (2-DG) or insulin on the levels of plasma FFA in conscious unrestrained rats. Microinjections of minute amounts (50 micrograms and 1 microliter) of 2-DG into the preoptic area of fed animals induced rapid increases in the concentration of plasma FFA. Microinjections of insulin (5 microU and 0.5 microliter) produced sharp decreases of the elevated plasma FFA levels in fasted rats. Both 2-DG and insulin induced small increases in plasma glucose that did not differ from similar increases induced by equal volumes of 0.15 M NaCl. The results provide direct evidence for the presence within the preoptic area of insulin-sensitive glucoreceptors involved in FFA mobilization. The data suggest that activation of these receptors and increased sympathetic outflow to adipose tissue contributes to fasting lipolysis.


2005 ◽  
Vol 289 (3) ◽  
pp. E482-E493 ◽  
Author(s):  
Luc J. C. van Loon ◽  
Michaela Thomason-Hughes ◽  
Dumitru Constantin-Teodosiu ◽  
René Koopman ◽  
Paul L. Greenhaff ◽  
...  

This study investigates the consequences of inhibition of adipose tissue lipolysis on skeletal muscle substrate use. Ten subjects were studied at rest and during exercise and subsequent recovery under normal, fasting conditions (control trial, CON) and following administration of a nicotinic acid analog (low plasma free fatty acid trial, LFA). Continuous [U-13C]palmitate and [6,6-2H2]glucose infusions were applied to quantify plasma free fatty acid (FFA) and glucose oxidation rates and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected to measure 1) fiber type-specific IMTG content; 2) allosteric regulators of hormone-sensitive lipase (HSL), glycogen phosphorylase, and pyruvate dehydrogenase; and 3) the phosphorylation status of HSL at Ser563 and Ser565. Administration of a nicotinic acid analog (acipimox) substantially reduced plasma FFA rate of appearance and subsequent plasma FFA concentrations ( P < 0.0001). At rest, this substantially reduced plasma FFA oxidation rates, which was compensated by an increase in the estimated IMTG use ( P < 0.05). During exercise, the progressive increase in FFA rate of appearance, uptake, and oxidation was prevented in the LFA trial and matched by greater IMTG and glycogen use. Differential phosphorylation of HSL or relief of its allosteric inhibition by long-chain fatty acyl-CoA could not explain the increase in muscle TG use, but there was evidence to support the contention that regulation may reside at the level of the glucose-fatty acid cycle. This study confirms the hypothesis that plasma FFA availability regulates both intramuscular lipid and glycogen use in vivo in humans.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2590
Author(s):  
Gregory C. Henderson

Plasma free fatty acid (FFA) concentration is elevated in obesity, insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and related comorbidities such as cardiovascular disease (CVD). Furthermore, experimentally manipulating plasma FFA in the laboratory setting modulates metabolic markers of these disease processes. In this article, evidence is presented indicating that plasma FFA is a disease risk factor. Elevations of plasma FFA can promote ectopic lipid deposition, IR, as well as vascular and cardiac dysfunction. Typically, elevated plasma FFA results from accelerated adipose tissue lipolysis, caused by a high adipose tissue mass, adrenal hormones, or other physiological stressors. Reducing an individual’s postabsorptive and postprandial plasma FFA concentration is expected to improve health. Lifestyle change could provide a significant opportunity for plasma FFA reduction. Various factors can impact plasma FFA concentration, such as chronic restriction of dietary energy intake and weight loss, as well as exercise, sleep quality and quantity, and cigarette smoking. In this review, consideration is given to multiple factors which lead to plasma FFA elevation and subsequent disruption of metabolic health. From considering a variety of medical conditions and lifestyle factors, it becomes clear that plasma FFA concentration is a modifiable risk factor for metabolic disease.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Krista A. Varady ◽  
Vi T. Dam ◽  
Monica C. Klempel ◽  
Matthew Horne ◽  
Rani Cruz ◽  
...  

1971 ◽  
Vol 49 (5) ◽  
pp. 394-398 ◽  
Author(s):  
W. D. Wagner ◽  
R. A. Peterson ◽  
R. J. Cenedella

Plasma free fatty acid (FFA) levels and the effects of prostaglandin E1 (PGE1) were studied in cold-acclimated and cold-exposed chickens and compared to controls. Chickens cold-acclimated at 4–7 or 8–11 °C for 4 weeks had significantly elevated plasma FFA when compared to the controls at 19–21 °C. Although PGE1 had no effect on the basal level of FFA of controls, a significantly lower plasma FFA was seen after injection of either 10 or 30 μg PGE1/kg in cold-acclimated chickens. Chickens cold-exposed to 2–3 °C for 4 h demonstrated significant elevations of plasma FFA when compared to controls. Only 30 μg PGE1/kg significantly depressed the plasma FFA in the cold-exposed birds. No inhibition of basal FFA release was seen in control animals. From these experiments, it is concluded that chickens mobilize FFA extensively under cold-exposure and that this stimulated lipolysis is inhibited by PGE1.


1968 ◽  
Vol 109 (5) ◽  
pp. 841-849 ◽  
Author(s):  
D. R. Wing ◽  
D S Robinson

1. The rise in clearing-factor lipase activity that occurs when epididymal fat bodies from starved rats are incubated in appropriate media in vitro is inhibited in the presence of 6-N-2′-O-dibutyryl-3′,5′-(cyclic)-AMP (1mm). 2. Inhibition occurs at a concentration of glucose in the incubation medium of 1·3mg./ml. or less, but not at a glucose concentration of 2·4mg./ml., unless caffeine (1mm), an inhibitor of 3′,5′-(cyclic)-nucleotide phosphodiesterase, is also present. Caffeine (5mm) alone inhibits the rise in clearing-factor lipase activity at a glucose concentration of 2·4mg./ml. of medium. 3. The concentration of free fatty acids in the epididymal fat bodies normally falls during incubations in vitro as the rise in clearing-factor lipase activity occurs. In the presence of 1mm-6-N-2′-O-dibutyryl-3′,5′-(cyclic)-AMP, however, either the tissue free fatty acid concentration is increased or it does not fall to the same extent. The concentration of glucose in the incubation medium is important in determining the direction and extent of the changes in tissue free fatty acid concentration that occur in the presence of 6-N-2′-O-dibutyryl-3′,5′-(cyclic)-AMP. 4. Free fatty acid concentrations in epididymal fat bodies in vivo rise as the clearing-factor lipase activity of the tissue falls during starvation. 5. The possibility that the concentration of 3′,5′-(cyclic)-AMP in adipose tissue may regulate clearing-factor lipase activity, and that the regulation may occur through effects of the nucleotide on tissue free fatty acid concentrations, is discussed.


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