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PMID:19293336

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Citation

Fowler, JD, Johnson, ND, Haroldson, TA, Brintnall, JA, Herrera, JE, Katz, SA and Bernlohr, DA (2009) Regulated renin release from 3T3-L1 adipocytes. Am. J. Physiol. Endocrinol. Metab. 296:E1383-91

Abstract

Whereas adipose tissue possesses a local renin-angiotensin system, the synthesis and regulated release of renin has not been addressed. To that end, we utilized differentiating 3T3-L1 cells and analyzed renin expression and secretion. Renin mRNA expression and protein enzymatic activity were not detectable in preadipocytes. However, upon differentiation, renin mRNA and both intracellular and extracellular renin activity were upregulated. In differentiated adipocytes, forskolin treatment resulted in a 28-fold increase in renin mRNA, whereas TNFalpha treatment decreased renin mRNA fourfold. IL-6, insulin, and angiotensin (Ang) II were without effect. In contrast, forskolin and TNFalpha each increased renin protein secretion 12- and sevenfold, respectively. Although both forskolin and TNFalpha induce lipolysis in adipocytes, fatty acids, prostaglandin E(2), and lipopolysaccharide had no effect on renin mRNA or secretion. To evaluate the mechanism(s) by which forskolin and/or TNFalpha are able to regulate renin secretion, a general lipase inhibitor (E600) and PKA inhibitor (H89) were used. Both inhibitors attenuated forskolin-induced renin release, whereas they had no effect on TNFalpha-regulated secretion. In contrast, E600 potentiated forskolin-stimulated renin mRNA levels, whereas H89 had no effect. Neither inhibitor had any influence on TNFalpha regulation of renin mRNA. Relative to lean controls, renin expression was reduced 78% in the epididymal adipose tissue of obese male C57Bl/6J mice, consistent with TNFalpha-mediated downregulation of renin mRNA in the culture system. In conclusion, the expression and secretion of renin are regulated under a complex series of hormonal and metabolic determinants in mature 3T3-L1 adipocytes.

Links

PubMed PMC2692391 Online version:10.1152/ajpendo.00025.2009

Keywords

3T3-L1 Cells; Adipocytes/cytology; Adipocytes/drug effects; Adipocytes/metabolism; Angiotensin II/pharmacology; Animals; Forskolin/pharmacology; Hypoglycemic Agents/pharmacology; Insulin/pharmacology; Interleukin-6/pharmacology; Isoquinolines/pharmacology; Lipolysis/drug effects; Lipolysis/physiology; Male; Mice; Mice, Inbred C57BL; Obesity/metabolism; Obesity/physiopathology; Protein Kinase Inhibitors/pharmacology; RNA, Messenger/metabolism; Renin/genetics; Renin/metabolism; Renin-Angiotensin System/physiology; Stem Cells/cytology; Stem Cells/drug effects; Stem Cells/metabolism; Sulfonamides/pharmacology; Tumor Necrosis Factor-alpha/pharmacology; Vasoconstrictor Agents/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:INS2

acts_upstream_of_or_within

GO:0010468: regulation of gene expression

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RENI1

enables

GO:0004175: endopeptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000136)

Seeded From UniProt

complete

MOUSE:RENI1

part_of

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000136)

Seeded From UniProt

complete

MOUSE:RENI1

acts_upstream_of_or_within

GO:0002018: renin-angiotensin regulation of aldosterone production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RENI1

acts_upstream_of_or_within

GO:0010033: response to organic substance

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TNFA

acts_upstream_of_or_within

GO:0050708: regulation of protein secretion

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000136)

Seeded From UniProt

complete

MOUSE:CATD

enables

GO:0004190: aspartic-type endopeptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000136)

Seeded From UniProt

complete

MOUSE:TNFA

acts_upstream_of_or_within

GO:0050708: regulation of protein secretion

ECO:0000314: direct assay evidence used in manual assertion

P

regulates_o_occurs_in:(CL:0000136)

Seeded From UniProt

complete


See also

References

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