Holloway 2014 Abstract MiP2014

Acute diet-induced insulin resistance is associated with increased adipose tissue mitochondrial ROS emissions.

Link:

Mitochondr Physiol Network 19.13 - MiP2014

Holloway GP, Ludzki AC, Root-McCaig J, Jain SS, Paglialunga S (2014)

Event: MiP2014

While it is widely accepted that consuming a high-fat diet (HFD) increases the risk of developing type II diabetes mellitus and obesity, little is known about the initiating factor causing insulin resistance. A recent study suggests that white adipose tissue (WAT) insulin sensitivity is drastically attenuated as early as one week on a HFD, however the underlying cause of this tissue specific insulin resistance is unknown as inflammation occurs many weeks later [1]. Since increased mitochondrial reactive oxygen species (ROS) and oxidative stress are associated with an insulin resistant state, we propose that elevated mitochondrial ROS emissions may be a causal factor in WAT insulin resistance. The aim of the current study was to determine mitochondrial respiration and ROS emission rates in WAT of mice under control and HFD conditions.

Adult male mice were placed on a standard chow (10% kcal fat) or a HFD (60% kcal fat) for one week. Mitochondrial respiration was measured by high-resolution respirometry in permeabilized adipose tissue. In addition, we optimized and validated a method to measure WAT mitochondrial ROS emissions.

One week on a HFD reduced glucose homeostasis, as WT HFD mice displayed increased plasma insulin levels as well as whole body insulin resistance determined by an intraperitoneal insulin tolerance test. While skeletal muscle insulin signaling was preserved, visceral WAT insulin signaling was reduced in WT HFD mice, confirming previous reports of acute HFD [1]. Moreover, we observed lipid-supported increased mtROS emissions in visceral WAT from WT HFD mice with no alterations in mitochondrial content or adipocyte cell size after one week of high-fat feeding, suggesting an early association between WAT mtROS emissions and insulin resistance.

In conclusion, we propose that elevated mtROS emission observed after one week of a HFD is a causal factor of WAT insulin resistance which contributes to altered whole body glucose homeostasis reported with an acute HFD.

• O2k-Network Lab: CA Guelph Holloway GP

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Diabetes, Obesity  Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Fat  Preparation: Permeabilized cells 

HRR: Oxygraph-2k  Event: B2, Oral  MiP2014 

Affiliation

1-Dept Human Health Nutritional Sci, Univ Guelph, Canada. - ghollowa@uoguelph.ca

References

1. Turner N, Kowalski GM, Leslie SJ, Risis S, Yang C, Lee-Young RS, Babb JR, Meikle PJ, Lancaster GI, Henstridge DC, White PJ, Kraegen EW, Marette A, Cooney GJ, Febbraio MA, Bruce CR (2013) Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding. Diabetologia 56: 1638-48.