Regulation and function of C1Q/TNF-related protein-5 (CTRP-5) in the context of adipocyte biology

Exp Clin Endocrinol Diabetes. 2013 May;121(5):310-7. doi: 10.1055/s-0032-1333299. Epub 2013 Feb 21.

Abstract

Background and aim: The C1q/TNF-related protein (CTRP) family represents a growing family of adiponectin paralogous proteins. CTRP-5 was detected in adipose tissue of mice and plays a role in the context of the metabolic syndrome. It was the aim to investigate the detailed expression profile of CTRP-5 in a variety of adipocytic cells and to determine whether CTRP-5 circulates in human serum. Moreover, regulation and function of CTRP-5 was studied in the context of adipocyte biology.

Material and methods: CTRP-5 serum levels were measured in 50 healthy subjects by ELISA. Genotype analysis was performed by direct sequencing in 200 probands. CTRP-5 mRNA and protein expression was analyzed by RT-PCR, real-time RT-PCR and Western blot. Recombinant CTRP-5 and fatty acids were used for stimulation experiments in 3T3-L1 adipocytes. siRNA-mediated knockdown of CTRP-3 was performed during adipocyte differentiation.

Results: CTRP-5 mRNA and protein was strongly expressed in a wide variety of human and murine adipocytic cells and was induced during adipocyte differentiation. Saturated fatty acids increased CTRP-5 expression in adipocytes. siRNA-mediated cellular knockdown of CTRP-3 in adipocytes resulted in an upregulation of CTRP-5 expression. CTRP-5 inhibited the release of resistin and adiponectin dose-dependently. CTRP-5 circulates abundantly in human sera with a broad interindividual variation. The SNP 1014 T/A was not associated with type 2 diabetes mellitus in 200 Caucasian probands.

Conclusions: CTRP-5 might be a novel adipokine that circulates abundantly in human sera. CTRP-5 is functionally involved in adipocyte biology and there might exist a counter-regulatory connection with its family member, CTRP-3.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Adipocytes / physiology*
  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Adult
  • Animals
  • Case-Control Studies
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Gene Frequency
  • Humans
  • Male
  • Membrane Proteins / blood
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Polymorphism, Single Nucleotide / physiology
  • RNA, Small Interfering / pharmacology
  • Young Adult

Substances

  • CTRP5 protein, mouse
  • Membrane Proteins
  • RNA, Small Interfering