Corrigendum to “Role of CaMKII in free fatty acid/hyperlipidemia-induced cardiac remodeling both in vitro and in vivo” [J. Mol. Cell. Cardiol. 109 (2017) 1–16]

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.

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Free fatty acid metabolism and obesity in man: In vivo in vitro comparisons

Metabolism ◽

10.1016/0026-0495(86)90006-5 ◽

1986 ◽

Vol 35 (6) ◽

pp. 505-514 ◽

Cited By ~ 62

Author(s):

S. Lillioja ◽

J. Foley ◽

C. Bogardus ◽

D. Mott ◽

B.V. Howard

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Free Fatty Acid Metabolism

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β-Adrenoceptors mediate inhibition of lipolysis in adipocytes of tilapia (Oreochromis mossambicus)

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00187.2001 ◽

2002 ◽

Vol 282 (2) ◽

pp. E318-E325 ◽

Cited By ~ 18

Author(s):

Gerjanne J. Vianen ◽

Peter P. Obels ◽

Guido E. E. J. M. van den Thillart ◽

Johan Zaagsma

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Free Fatty Acid ◽

Plasma Free Fatty Acid ◽

Oreochromis Mossambicus ◽

Plasma Norepinephrine ◽

In Vivo Experiments ◽

First Time

The regulation of triglyceride mobilization by catecholamines was investigated in the teleost fish Oreochromis mossambicus (tilapia) in vivo and in vitro. In vitro experiments were carried out with adipocytes that were isolated for the first time from fish adipose tissue. For the in vivo experiments, cannulated tilapia were exposed to stepwise decreasing oxygen levels (20, 10, and 5% air saturation; 3.9, 1.9, and 1.0 kPa Po 2, respectively), each level being maintained for 2 h. Blood samples were taken at timed intervals and analyzed for plasma lactate, glucose, free fatty acids, epinephrine, norepinephrine, and cortisol. Hypoxia exposure did not change plasma epinephrine levels. In contrast, the plasma norepinephrine concentration markedly increased at all hypoxia levels. Over the same period, plasma free fatty acid levels showed a significant continuous decrease, suggesting that norepinephrine is responsible for the reduced plasma free fatty acid concentration, presumably through inhibition of lipolysis in adipose tissue. To elucidate the mechanism, adipocytes were isolated from mesenteric adipose tissue of tilapia and incubated with 1) norepinephrine, 2) norepinephrine + phentolamine (α1,α2-antagonist), 3) isoproterenol (nonselective β-agonist), 4) isoproterenol + timolol (β1,β2-antagonist), 5) norepinephrine + timolol, and 6) BRL-35135A (β3-agonist). The results demonstrate for the first time that norepinephrine and isoproterenol suppress lipolysis in isolated adipocytes of tilapia. The effect of norepinephrine is not mediated through α2-adrenoceptors but, like isoproterenol, via β-adrenoceptors. Furthermore, this study provides strong indications that β3-adrenoceptors are involved.

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An ethanolic extract of Artemisia scoparia inhibits lipolysis in vivo and has antilipolytic effects on murine adipocytes in vitro

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00177.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. E1053-E1061 ◽

Cited By ~ 4

Author(s):

Anik Boudreau ◽

Allison J. Richard ◽

Jasmine A. Burrell ◽

William T. King ◽

Ruth Dunn ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Free Fatty Acid ◽

Microarray Analysis ◽

High Fat Diet ◽

Ethanolic Extract ◽

High Fat ◽

Artemisia Scoparia

An ethanolic extract of Artemisia scoparia (SCO) has metabolically favorable effects on adipocyte development and function in vitro and in vivo. In diet-induced obese mice, SCO supplementation significantly reduced fasting glucose and insulin levels. Given the importance of adipocyte lipolysis in metabolic health, we hypothesized that SCO modulates lipolysis in vitro and in vivo. Free fatty acids and glycerol were measured in the sera of mice fed a high-fat diet with or without SCO supplementation. In cultured 3T3-L1 adipocytes, the effects of SCO on lipolysis were assessed by measuring glycerol and free fatty acid release. Microarray analysis, qPCR, and immunoblotting were used to assess gene expression and protein abundance. We found that SCO supplementation of a high-fat diet in mice substantially reduces circulating glycerol and free fatty acid levels, and we observed a cell-autonomous effect of SCO to significantly attenuate tumor necrosis factor-α (TNFα)-induced lipolysis in cultured adipocytes. Although several prolipolytic and antilipolytic genes were identified by microarray analysis of subcutaneous and visceral adipose tissue from SCO-fed mice, regulation of these genes did not consistently correlate with SCO’s ability to reduce lipolytic metabolites in sera or cell culture media. However, in the presence of TNFα in cultured adipocytes, SCO induced antilipolytic changes in phosphorylation of hormone-sensitive lipase and perilipin. Together, these data suggest that the antilipolytic effects of SCO on adipose tissue play a role in the ability of this botanical extract to improve whole body metabolic parameters and support its use as a dietary supplement to promote metabolic resiliency.

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Acyl-CoA thioesterase 1 prevents cardiomyocytes from Doxorubicin-induced ferroptosis via shaping the lipid composition

Cell Death and Disease ◽

10.1038/s41419-020-02948-2 ◽

2020 ◽

Vol 11 (9) ◽

Author(s):

Yunchang Liu ◽

Liping Zeng ◽

Yong Yang ◽

Chen Chen ◽

Daowen Wang ◽

...

Keyword(s):

Fatty Acid ◽

Lipid Composition ◽

Cardiac Injury ◽

Leading Edge ◽

Heart Tissue ◽

Protective Role ◽

Enzymatic Function

Abstract In this study, we first established the doxorubicin-induced cardiotoxicity (DIC) model with C57BL/6 mice and confirmed cardiac dysfunction with transthoracic echocardiography examination. RNA-sequencing was then performed to explore the potential mechanisms and transcriptional changes in the process. The metabolic pathway, biosynthesis of polyunsaturated fatty acid was significantly altered in DOX-treated murine heart, and Acot1 was one of the leading-edge core genes. We then investigated the role of Acot1 to ferroptosis that was reported recently to be related to DIC. The induction of ferroptosis in the DOX-treated heart was confirmed by transmission electron microscopy, and the inhibition of ferroptosis using Fer-1 effectively prevented the cardiac injury as well as the ultrastructure changes of cardiomyocyte mitochondrial. Both in vitro and in vivo experiments proved the downregulation of Acot1 in DIC, which can be partially prevented with Fer-1 treatment. Overexpression of Acot1 in cell lines showed noteworthy protection to ferroptosis, while the knock-down of Acot1 sensitized cardiomyocytes to ferroptosis by DIC. Finally, the heart tissue of αMHC-Acot1 transgenic mice presented altered free fatty acid composition, indicating that the benefit of Acot1 in the inhibition of ferroptosis lies biochemically and relates to its enzymatic function in lipid metabolism in DIC. The current study highlights the importance of ferroptosis in DIC and points out the potential protective role of Acot1 in the process. The beneficial role of Acot1 may be related to its biochemical function by shaping the lipid composition. In all, Acot1 may become a potential treating target in preventing DIC by anti-ferroptosis.

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Acute metabolic effects of adrenergic agents in swine

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.252.1.e85 ◽

1987 ◽

Vol 252 (1) ◽

pp. E85-E95 ◽

Cited By ~ 2

Author(s):

H. J. Mersmann

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Free Fatty Acid ◽

Plasma Free Fatty Acid ◽

Metabolic Effects ◽

Adipose Tissue Lipolysis ◽

Beta 2 ◽

Stimulation Of

A pig model in vivo was used to confirm the unique specificity for stimulation of porcine adipose tissue lipolysis by norepinephrine analogues in vitro. Plasma free fatty acid and blood glycerol concentrations were monitored as probable indicators of adipose tissue lipolysis. Plasma glucose and lactate concentrations, blood pressure, and heart rate were monitored also. Norepinephrine analogues were infused intravenously. Several compounds, classified as either beta 1- or beta 2-adrenergic agonists, that stimulated lipolysis in vitro also increased plasma free fatty acid and blood glycerol concentrations in vivo. Tazolol (beta 1) and quinterenol (beta 2) did not stimulate lipolysis in vitro and likewise did not elevate plasma free fatty acid or blood glycerol concentrations in vivo. Clenbuterol and zinterol did not stimulate lipolysis in vitro but elevated plasma free fatty acid concentrations in vivo, implying indirect effects. Isoproterenol stimulation of plasma free fatty acid and blood glycerol concentrations in vivo was antagonized by propranolol, implying the beta-adrenergic nature of the receptors. Infusion of purported beta 1- and beta 2-adrenergic antagonists suggested control of lipolysis in vivo predominantly by beta 1-adrenergic receptors; however, because the results in vitro do not indicate this specificity, differential pharmacodynamics of the antagonists are suggested rather than designation of receptor subtypes. There was no evidence for alpha-adrenergic mediated inhibition of adipose tissue lipolysis in vivo, confirming observations in vitro.

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Utilization of free fatty acids by diaphragm in vitro

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1962.203.2.311 ◽

1962 ◽

Vol 203 (2) ◽

pp. 311-315 ◽

Cited By ~ 88

Author(s):

P. T. Bodel ◽

D. Rubinstein ◽

E. E. McGarry ◽

J. C. Beck

Keyword(s):

Fatty Acids ◽

Growth Hormone ◽

Fatty Acid ◽

Free Fatty Acid ◽

Free Fatty Acids ◽

Gastrocnemius Muscle ◽

Rat Diaphragm ◽

Diaphragm In Vitro

Human and rat diaphragm and rat gastrocnemius muscle oxidize and esterify palmitate-1-C14. Incorporation of C14 was found to be in proportion to the palmitate present in the medium over a range of concentrations from 0.8 to 2.9 µEq/ml. Fasting increased C14O2 production but had no effect on esterification. Iodoacetate or an atmosphere of nitrogen inhibited esterification of palmitate but increased the amount of free fatty acid in the tissue. Insulin increased esterification, and this was enhanced by the addition of glucose. Glucose and insulin exerted a sparing action on the oxidation of glycerides by a tissue previously charged with palmitate-1-C14. Growth hormone administered in vivo over a period of 1 week or in vitro during incubation had no effect on esterification or metabolism of palmitate-1-C14.

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Loss of Intestine-Specific FFA3 Has Protective Effects Against Diet-Induced Obesity and Hyperglycemia in Mice on a Western Diet

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.901 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A441-A441

Author(s):

Kristen Roan Lednovich ◽

Sophie Gough ◽

Medha Priyadarshini ◽

Brian T Layden

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Glycemic Control ◽

Knockout Mouse ◽

Western Diet ◽

Metabolic Homeostasis ◽

Normal Chow ◽

Free Fatty Acid Receptor

Abstract Free fatty acid receptor 3 (FFA3) is a recently-deorphaned G protein-coupled receptor belonging to the free fatty acid receptor family. Its ligands are short-chain fatty acids (SCFAs), which are key nutrients that play a diverse role in physiological function, including the regulation of metabolic homeostasis and glycemic control. FFA3 is broadly expressed in a multitude of tissues including the intestine, pancreas, and central nervous system, and is thought to contribute to metabolic homeostasis via a summation of its tissue-specific effects. Consequently, FFA3 has been identified as a potential drug target for metabolic diseases including obesity and type-2 diabetes. FFA3 is highly expressed in enteroendocrine cells (EECs) within the intestinal epithelium - the major site of SCFA generation - and is hypothesized to play a role in the secretion of postprandial incretin hormones, which are a group of specialized gut peptides that regulate a variety of metabolic and digestive functions following a meal. However, due to a paucity of data, the role of FFA3 within the intestine and its effects on physiology and metabolism is largely unclear. Previous in vivo studies involving this receptor have largely relied on global knockout mouse models, making it difficult to isolate its effects in EECs. To overcome this challenge, we have generated a novel intestine-specific knockout mouse model for FFA3, utilizing Cre-mediated recombination under the expression of the villin promoter. Here, we report the first in vivo characterization of FFA3 in the intestine and reveal novel insights into receptor function. Following model validation, we conducted a general metabolic assessment of male Villin-Cre-FFA3 mice on normal chow and observed no major congenital or time-dependent defects. Because dietary changes are known to alter gut microbial composition, and thereby SCFA production, a pilot study was performed on male Villin-Cre-FFA3 mice and their littermate controls to probe for a phenotype on a high-fat, high-sugar “western diet.” Mice were placed on either normal chow (NC) or western diet (WD) at 10 weeks of age and metabolically profiled for 25 weeks. Our data reveals that Villin-Cre-FFA3 mice on WD, but not NC, were protected from diet-induced metabolic dysfunction, and displayed significantly lower levels of fat mass as well as modestly improved glycemic control. Our findings suggest a novel role of FFA3 in mediating the metabolic consequences of a western diet - a state of high inflammation, dysbiosis and metabolic stress. Moreover, these data support an intestine-specific role of FFA3 in both glucose and lipid metabolism, and further suggest the receptor’s role in whole-body metabolic homeostasis and in the development of adiposity and hyperglycemia.

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