The role of free fatty acids in the regulation of lipolysis by human adipose tissue cells

Burns, Thomas W.; Langley, Paul E.; Terry, Boyd E.; Robinson, Gail

doi:10.1016/0026-0495(78)90261-5

Cited by 31 publications

(21 citation statements)

References 14 publications

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“…Since the 1970s, it has been known that agonist-induced adipose lipolysis is inhibited by the LCFA generated through lipolysis and that it requires constant removal of free nonesterifi ed fatty acids by their binding to medium albumin or by frequent medium replacement ( 4,5 ). However, the mode of inhibition of agonist-induced lipolysis by its LCFA end product remained to be resolved.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to M ␤ ␤ , inhibition of agonist-induced lipolysis by AICAR is proposed to be solely accounted for by suppression of Raf1 expression by ZMP-activated AMPK. As MEDICA analogs simulate the characteristics of LCFA in terms of AMPK activation ( 12 ) and in inducing UPR ( 27,28 ), we may assume that the mode of action proposed for MEDICA may account, at least partially, for inhibition of agonist-induced lipolysis by LCFA ( 4,5 ). In light of AMPK activation by metformin or octanoate ( 31,32 ), the proposed transduction pathway may also offer a mode of action for the recently reported activity of metformin ( 31 ) or octanoate ( 32 ) in suppressing isoproterenol-induced lipolysis in primary rat adipocytes or 3T3-L1 adipocytes, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Phosphorylated and total protein blots were carried out using the same lysates. Blots were probed with the indicated fi rst antibody, followed by horseradish ( 4,5 ). The mode of action of LCFA in suppressing agonistinduced lipolysis still remains to be investigated, being ascribed to product inhibition of HSL by its association with fatty acid-bound aP2 ( 6 ), or alternatively, to futile cycling of LCFA between lipolysis and reesterifi cation ( 7 ).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…1 ) and in analogy to natural LCFA in vitro ( 4,5 ), isoproterenol-induced lipolysis of 3T3-L1 adipocytes was robustly inhibited by M ␤ ␤ ( Fig. 2A ), as well as by other MEDICA analogs (not shown).…”

Section: Inhibition Of Isoproterenol-induced Lipolysis By M ␤ ␤mentioning

confidence: 99%

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Suppression of adipose lipolysis by long-chain fatty acid analogs

Kalderon

Azazmeh

Azulay

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org lipoproteins. Agonist-induced lipolysis is mediated by consecutive activation of the adenylate cyclase (AC), resulting in cAMP production and protein kinase A (PKA) activation by cAMP, followed by PKA-induced phosphorylation of hormone-sensitive lipase (HSL) at three serine residues (563, 659, and 660), resulting in its activation and translocation from the cytosol to the lipid-droplet surface. Concomitant with HSL phosphorylation, the phosphorylation of perilipin by PKA at multiple sites (S81, S222, S276, and S517) results in a dynamic restructuring of the lipid-droplet surface, in facilitating the translocation of phosphorylated HSL to the lipid droplet, and in activating its hydrolyzing activity. Perilipin phosphorylation by PKA further results in releasing CGI-58 from the lipid droplet, in its association with adipose triacylglycerol lipase (ATGL), and in activating its lipolytic activity. Activated ATGL, HSL, and monoglyceride lipase may act now consecutively in hydrolyzing adipose triacyglycerols to diacylglycerol, monoacylglycerol, and fi nally to free glycerol and LCFA. Agonist-induced cAMP and lipolysis is restrained by insulin due to cAMP hydrolysis by insulin-activated phosphodiesterase3B (PDE3B) ( 2 ), combined with insulin-induced reesterifi cation of LCFA into adipose fat (reviewed in Ref.3 ). Indeed, increased adipose effl ux of free LCFA, due to increased adipose lipolysis and/or suppression of adipose LCFA reesterifi cation, is considered a cornerstone of diabetes. Agonist-induced lipolysis is further robustly inhibited by the LCFA generated during lipolysis ( 4, 5 ). In fact, agonist-induced lipolysis is made possible only by removing the free nonesterifi ed LCFA product through their binding to medium albumin or by frequent medium replacement Lipolysis of adipose fat stores results in the production of nonesterifi ed long-chain fatty acids (LCFA) in response to changes in energy requirements and availability (reviewed in Ref. 1 ). Fatty acids derived by adipose fat lipolysis may either be reesterifi ed into adipose fat, or serve as major source of oxidizable substrate for muscle activity and as precursor for the hepatic production of triacylglycerol-richFunded by Eurostars project E!5138.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

Section: Inhibition Of Isoproterenol-induced Lipolysis By M ␤ ␤mentioning

confidence: 99%

See 2 more Smart Citations

Suppression of adipose lipolysis by long-chain fatty acid analogs

Kalderon

Azazmeh

Azulay

et al. 2012

Journal of Lipid Research

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“…Although the etiology ofthis discrepancy is not known, failure to increase forearm blood flow may have contributed to this effect. Increased FFA concentrations can inhibit lipolysis (32), and either increased FFA delivery or decreased removal of locally produced FFA may have inhibited forearm lipolysis. Whether the modest blood flow reductions observed were caused by local vasoconstriction secondary to high FFA/albumin ratios (33), a direct effect of the somatostatin, or hypoinsulinemia itself is unknown.…”

Section: Discussionmentioning

confidence: 99%

Regulation of forearm lipolysis in different types of obesity. In vivo evidence for adipocyte heterogeneity.

Jensen¹

1991

J. Clin. Invest.

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Forearm and systemic adipose tissue free fatty acid (FFA) release was measured in eight nonobese, six lower-body obese, and eight upper-body obese women under basal, hyperinsulinemic, and hypoinsulinemic conditions to determine whether forearm fat is regulated in a similar manner as whole body fat. Results: Adipose tissue palmitate release was greater from forearm than whole body (5.97±0.75 vs. 3.84±0.34 gmol -kg far' -min-', respectively, P < 0.005, n = 22 subjects). Systemic palmitate release, relative to fat mass, was significantly (P < 0.01) greater in nonobese than upper-body obese, and upper-body obese than lower-body obese women, and forearm adipose tissue palmitate release followed the same pattern. Hyperinsulinemia suppressed systemic and forearm lipolysis to similar degrees, however, hypoinsulinemia consistently increased systemic palmitate flux without increasing forearm palmitate release. These results confirm the heterogeneity of adipose tissue in an in vivo model and emphasize the need to consider which adipose tissue depots are responsible for the differences in systemic FFA flux in obese and nonobese humans. (J. Clin. Invest. 1991. 87:187-193.).

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Alterations of Long-Chain Free Fatty Acid and Magnesium Concentrations in Acute Myocardial Infarction

Flink¹

1981

Arch Intern Med

107

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The role of free fatty acids in the regulation of lipolysis by human adipose tissue cells

Cited by 31 publications

References 14 publications

Suppression of adipose lipolysis by long-chain fatty acid analogs

Suppression of adipose lipolysis by long-chain fatty acid analogs

Regulation of forearm lipolysis in different types of obesity. In vivo evidence for adipocyte heterogeneity.

Alterations of Long-Chain Free Fatty Acid and Magnesium Concentrations in Acute Myocardial Infarction

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