AIMS/HYPOTHESIS: Proinflammatory immune cell infiltration in human adipose tissue is associated with the development of insulin resistance. We previously identified, via a gene expression-based genome-wide association study, the cell-surface immune cell receptor CD44 as a functionally important gene associated with type 2 diabetes. We then showed that, compared with controls, Cd44 knockout mice were protected from insulin resistance and adipose tissue inflammation during diet-induced obesity. We thus sought to test whether CD44 is associated with adipose tissue inflammation and insulin resistance in humans. METHODS: Participants included 58 healthy, overweight/moderately obese white adults who met predetermined criteria for insulin resistance or insulin sensitivity based on the modified insulin-suppression test. Serum was collected from 43 participants to measure circulating concentrations of CD44. Subcutaneous adipose tissue was obtained from 17 participants to compare CD44, its ligand osteopontin (OPN, also known as SPP1) and pro-inflammatory gene expression. CD44 expression on adipose tissue macrophage (ATM) surfaces was determined by flow cytometry. RESULTS: Serum CD44 concentrations were significantly increased in insulin-resistant (IR) participants. CD44 gene expression in subcutaneous adipose tissue was threefold higher in the IR subgroup. The expression of OPN, CD68 and IL6 was also significantly elevated in IR individuals. CD44 gene expression correlated significantly with CD68 and IL6 expression. CD44 density on ATMs was associated with proinflammatory M1 polarisation. CONCLUSIONS/ INTERPRETATION: CD44 and OPN in human adipose tissue are associated with localised inflammation and systemic insulin resistance. This receptor-ligand pair is worthy of further research as a potentially modifiable contributor to human insulin resistance and type 2 diabetes.
AIMS/HYPOTHESIS: Proinflammatory immune cell infiltration in human adipose tissue is associated with the development of insulin resistance. We previously identified, via a gene expression-based genome-wide association study, the cell-surface immune cell receptor CD44 as a functionally important gene associated with type 2 diabetes. We then showed that, compared with controls, Cd44 knockout mice were protected from insulin resistance and adipose tissue inflammation during diet-induced obesity. We thus sought to test whether CD44 is associated with adipose tissue inflammation and insulin resistance in humans. METHODS:Participants included 58 healthy, overweight/moderately obese white adults who met predetermined criteria for insulin resistance or insulin sensitivity based on the modified insulin-suppression test. Serum was collected from 43 participants to measure circulating concentrations of CD44. Subcutaneous adipose tissue was obtained from 17 participants to compare CD44, its ligand osteopontin (OPN, also known as SPP1) and pro-inflammatory gene expression. CD44 expression on adipose tissue macrophage (ATM) surfaces was determined by flow cytometry. RESULTS: Serum CD44 concentrations were significantly increased in insulin-resistant (IR) participants. CD44 gene expression in subcutaneous adipose tissue was threefold higher in the IR subgroup. The expression of OPN, CD68 and IL6 was also significantly elevated in IR individuals. CD44 gene expression correlated significantly with CD68 and IL6 expression. CD44 density on ATMs was associated with proinflammatory M1 polarisation. CONCLUSIONS/ INTERPRETATION:CD44 and OPN in human adipose tissue are associated with localised inflammation and systemic insulin resistance. This receptor-ligand pair is worthy of further research as a potentially modifiable contributor to humaninsulin resistance and type 2 diabetes.
Authors: Maximilian Zeyda; Karina Gollinger; Jelena Todoric; Florian W Kiefer; Maike Keck; Oskar Aszmann; Gerhard Prager; Gerhard J Zlabinger; Peter Petzelbauer; Thomas M Stulnig Journal: Endocrinology Date: 2011-04-05 Impact factor: 4.736
Authors: John M Wentworth; Gaetano Naselli; Wendy A Brown; Lisa Doyle; Belinda Phipson; Gordon K Smyth; Martin Wabitsch; Paul E O'Brien; Leonard C Harrison Journal: Diabetes Date: 2010-03-31 Impact factor: 9.461
Authors: Javier Gómez-Ambrosi; Victoria Catalán; Beatriz Ramírez; Amaia Rodríguez; Inmaculada Colina; Camilo Silva; Fernando Rotellar; Carmen Mugueta; María J Gil; Javier A Cienfuegos; Javier Salvador; Gema Frühbeck Journal: J Clin Endocrinol Metab Date: 2007-06-26 Impact factor: 5.958
Authors: Baoqian Zhu; Keiko Suzuki; Harvey A Goldberg; Susan R Rittling; David T Denhardt; Christopher A G McCulloch; Jaro Sodek Journal: J Cell Physiol Date: 2004-01 Impact factor: 6.384
Authors: T McLaughlin; A Sherman; P Tsao; O Gonzalez; G Yee; C Lamendola; G M Reaven; S W Cushman Journal: Diabetologia Date: 2007-06-05 Impact factor: 10.122
Authors: Charlotte E Egan; Erin K Daugherity; Arlin B Rogers; Delbert S Abi Abdallah; Eric Y Denkers; Kirk J Maurer Journal: PLoS One Date: 2013-06-07 Impact factor: 3.240
Authors: Annie Hasib; Chandani K Hennayake; Deanna P Bracy; Aimée R Bugler-Lamb; Louise Lantier; Faisel Khan; Michael L J Ashford; Rory J McCrimmon; David H Wasserman; Li Kang Journal: Am J Physiol Endocrinol Metab Date: 2019-09-24 Impact factor: 4.310
Authors: Nadine Nagy; Vivekananda G Sunkari; Gernot Kaber; Sonia Hasbun; Dung N Lam; Cate Speake; Srinath Sanda; Tracey L McLaughlin; Thomas N Wight; Steven R Long; Paul L Bollyky Journal: Matrix Biol Date: 2018-09-06 Impact factor: 11.583