OBJECTIVE: COL6A3 may modulate adipose tissue function in obesity and insulin resistance. A role for human adipocytes linking COL6A3 with insulin resistance warrants exploration. METHODS: COL6A3 mRNA in abdominal subcutaneous adipose samples was compared between (1) BMI-matched obese subjects resistant or sensitive to insulin (surgical whole tissue biopsies, n = 30/group), (2) lean/overweight and obese subjects (isolated adipocytes from collagenase-treated surgical biopsies, n = 11/group), (3) developing primary human adipocytes with/without knockdown of the insulin-sensitizing adipogenic gene PPARG (collagenase-treated lipoaspirate, n = 5), and (4) small and large adipocytes from lean/overweight subjects (collagenase-treated surgical biopsies or lipoaspirate, n = 10). Insulin resistance and sensitivity were assessed by euglycemic-hyperinsulinemic clamp (glucose infusion rate <60 and >70 μmol kg(-1) min(-1) , respectively) (1), or by HOMA-IR and TG/HDL ratio (2). RESULTS: Whole tissue COL6A3 mRNA was 2.6-fold higher in insulin resistant compared to sensitive subjects (P < 0.001). In isolated adipocytes, COL6A3 mRNA correlated positively with BMI (P = 0.007), HOMA-IR (P = 0.039), and TG/HDL (P = 0.004). PPARG knockdown in developing adipocytes increased COL6A3 mRNA 1.5-fold (P = 0.043). The inverse relationship with adipocyte development was further supported by 2.8-fold higher COL6A3 mRNA in small compared to large adipocytes (P = 0.004). CONCLUSION: Increased adipocyte COL6A3 expression associates with insulin resistance in humans, which may involve impaired PPARγ-mediated adipocyte development.
OBJECTIVE:COL6A3 may modulate adipose tissue function in obesity and insulin resistance. A role for human adipocytes linking COL6A3 with insulin resistance warrants exploration. METHODS:COL6A3 mRNA in abdominal subcutaneous adipose samples was compared between (1) BMI-matched obese subjects resistant or sensitive to insulin (surgical whole tissue biopsies, n = 30/group), (2) lean/overweight and obese subjects (isolated adipocytes from collagenase-treated surgical biopsies, n = 11/group), (3) developing primary human adipocytes with/without knockdown of the insulin-sensitizing adipogenic gene PPARG (collagenase-treated lipoaspirate, n = 5), and (4) small and large adipocytes from lean/overweight subjects (collagenase-treated surgical biopsies or lipoaspirate, n = 10). Insulin resistance and sensitivity were assessed by euglycemic-hyperinsulinemic clamp (glucose infusion rate <60 and >70 μmol kg(-1) min(-1) , respectively) (1), or by HOMA-IR and TG/HDL ratio (2). RESULTS: Whole tissue COL6A3 mRNA was 2.6-fold higher in insulin resistant compared to sensitive subjects (P < 0.001). In isolated adipocytes, COL6A3 mRNA correlated positively with BMI (P = 0.007), HOMA-IR (P = 0.039), and TG/HDL (P = 0.004). PPARG knockdown in developing adipocytes increased COL6A3 mRNA 1.5-fold (P = 0.043). The inverse relationship with adipocyte development was further supported by 2.8-fold higher COL6A3 mRNA in small compared to large adipocytes (P = 0.004). CONCLUSION: Increased adipocyte COL6A3 expression associates with insulin resistance in humans, which may involve impaired PPARγ-mediated adipocyte development.
Authors: Lindsey A Muir; Christopher K Neeley; Kevin A Meyer; Nicki A Baker; Alice M Brosius; Alexandra R Washabaugh; Oliver A Varban; Jonathan F Finks; Brian F Zamarron; Carmen G Flesher; Joshua S Chang; Jennifer B DelProposto; Lynn Geletka; Gabriel Martinez-Santibanez; Niko Kaciroti; Carey N Lumeng; Robert W O'Rourke Journal: Obesity (Silver Spring) Date: 2016-03 Impact factor: 5.002
Authors: A Michaud; J Tordjman; M Pelletier; Y Liu; S Laforest; S Noël; G Le Naour; C Bouchard; K Clément; A Tchernof Journal: Int J Obes (Lond) Date: 2016-10-04 Impact factor: 5.095
Authors: Joseph W Beals; Gordon I Smith; Mahalakshmi Shankaran; Anja Fuchs; George G Schweitzer; Jun Yoshino; Tyler Field; Marcy Matthews; Edna Nyangau; Darya Morozov; Bettina Mittendorfer; Marc K Hellerstein; Samuel Klein Journal: Hepatology Date: 2021-06-22 Impact factor: 17.425