Bodis 2019 J Clin Endocrinol Metab
|Bodis K, Jelenik T, Lundbom J, Markgraf DF, Strom A, Zaharia OP, Karusheva Y, Burkart V, Muessig K, Kupriyanova Y, Ouni M, Wolkersdorfer M, Hwang JH, Ziegler D, Schuermann A, Roden M, Szendroedi J (2019) Expansion and impaired mitochondrial efficiency of deep subcutaneous adipose tissue in recent-onset type 2 diabetes. J Clin Endocrinol Metab 105:dgz267.|
Bodis K, Jelenik T, Lundbom J, Markgraf DF, Strom A, Zaharia OP, Karusheva Y, Burkart V, Muessig K, Kupriyanova Y, Ouni M, Wolkersdorfer M, Hwang JH, Ziegler D, Schuermann A, Roden M, Szendroedi J (2019) J Clin Endocrinol Metab
Abstract: Impaired adipose tissue (AT) function might induce recent-onset type 2 diabetes (T2D). Understanding AT energy metabolism could yield novel targets for the treatment of T2D.
Recently diagnosed male T2D patients and healthy humans (controls, CON) of similar abdominal subcutaneous AT (SAT)-thickness, fat mass and age (n=14 each), underwent hyperinsulinemic-euglycemic clamps with [6,6-2H2]glucose and indirect calorimetry. We assessed mitochondrial efficiency (coupling: state 3/4o; proton leak: state 4o/u) via high-resolution respirometry in superficial (SSAT) and deep (DSAT) SAT-biopsies, hepatocellular lipids (HCL) and fat mass by proton-magnetic-resonance-spectroscopy and -imaging.
T2D patients (known diabetes duration: 2.5 [0.1; 5.0] years) had 43%, 44% and 63% lower muscle insulin sensitivity (IS), metabolic flexibility (p<0.01) and AT IS (p<0.05), 73% and 31% higher HCL (p<0.05) and DSAT-thickness (p<0.001), but similar hepatic IS compared to CON. Mitochondrial efficiency was ~22% lower in SSAT and DSAT of T2D (p<0.001) and ~8% lower in SSAT vs DSAT (p<0.05). In both fat depots, mitochondrial coupling correlated positively with muscle IS and metabolic flexibility (r≥0.40, p<0.05), proton leak correlated positively (r≥0.51, p<0.01) and oxidative capacity negatively (r≤-0.47, p<0.05) with fasting FFA. Metabolic flexibility correlated positively with SAT-oxidative capacity (r≥0.48, p<0.05) and negatively with DSAT-thickness (r=-0.48, p<0.05). DSAT-thickness correlated negatively with mitochondrial coupling in both depots (r≤-0.50, p<0.01) and muscle IS (r=-0.59, p<0.01), positively with FFA during clamp (r=0.63, p<0.001) and HCL (r=0.49, p<0.01).
Impaired mitochondrial function, insulin resistance and DSAT expansion are AT abnormalities in recent-onset T2D that might promote whole-body insulin resistance and increased substrate flux to the liver.
© Endocrine Society 2019. • Keywords: Adipose tissue, Humans, Insulin resistance, Metabolic flexibility, Mitochondrial function, Type 2 diabetes • Bioblast editor: Plangger M • O2k-Network Lab: DE Duesseldorf Roden M
Labels: MiParea: Respiration, Patients Pathology: Diabetes
Organism: Human Tissue;cell: Fat Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, NS HRR: Oxygraph-2k