Insulin sensitivity is preserved in mice made obese by feeding a high starch diet

  1. Amanda E Brandon  Is a corresponding author
  2. Lewin Small
  3. Tuong-Vi Nguyen
  4. Eurwin Suryana
  5. Henry Gong
  6. Christian Yassmin
  7. Sarah E Hancock
  8. Tamara Pulpitel
  9. Sophie Stonehouse
  10. Letisha Prescott
  11. Melkam A Kebede
  12. Belinda Yau
  13. Lake-Ee Quek
  14. Greg M Kowalski
  15. Clinton R Bruce
  16. Nigel Turner
  17. Gregory J Cooney
  1. School of Medical Sciences, University of Sydney, Australia
  2. Diabetes and Metabolism Division, Garvan Institute of Medical Research, Australia
  3. Department of Pharmacology, School of Medical Sciences, University of New South Wales, Australia
  4. School of Life and Environmental Sciences, Charles Perkins Centre, University of Sydney, Australia
  5. School of Mathematics and Statistics, Charles Perkins Centre, University of Sydney, Australia
  6. Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Australia
  7. Metabolic Research Unit, School of Medicine, Deakin University, Australia
6 figures, 1 table and 4 additional files

Figures

High starch (Hi-ST) and high fat (Hi-F) similarly increase body weight, fat mass, and food intake without changes in lean mass or energy expenditure.

(A) Body weight, n=18–20, (B) lean mass, (C) fat mass, n=8–10, (D) food intake, n=4 (averaged within cages), (E) energy expenditure, (F) 24 hr average of energy expenditure, (G) relationship between …

Glucose tolerance of high starch (Hi-ST) mice is similar to chow despite increased adiposity and may be due to liver, but not β-cell, involvement.

(A) Oral glucose tolerance test (oGTT) after 4 weeks of feeding, (B) area under the curve for the oGTT after 4 weeks of feeding, n=45, (C) insulin released during the oGTT after 4 weeks of feeding, …

Euglycaemic-hyperinsulinaemic clamp parameters show preservation of whole body, liver and skeletal muscle insulin resistance.

(A) Blood glucose, (B) plasma insulin, (C) glucose infusion rate, (D) average glucose infusion rate of 90–120 min, (E) whole body glucose disappearance, (F) hepatic glucose output (HGO), (G) percent …

Adipose tissue weights, and adipocyte size, were increased to a similar extent in high starch (Hi-ST) and high fat (Hi-F) as were plasma leptin and the level of triglycerides in liver and muscle.

(A) Tissue weights, n=9–11, (B) average adipocyte size in epididymal white adipose tissue (WAT), (C) average adipocyte size in subcutaneous WAT, n=3–5, plasma levels of (D) leptin and (E) …

The increased liver triglycerides in the high starch (Hi-ST) mice was due to an upregulation of the de novo lipogenic pathway.

(A) Liver triglycerides, (B) liver lipogenic rate, (C) brown adipose tissue (BAT) lipogenic rate, (D) white adipose tissue (WAT) lipogenic rates, n=12–15, (E) western blots of acetyl CoA carboxylase …

Figure 6 with 2 supplements
Reduction in total ceramide levels, as well as specific ceramide species that are correlated with insulin sensitivity, is found in the liver and quadriceps muscle of high starch (Hi-ST) fed mice.

(A) Total lipid levels, (B) diacylglycerol (DAG) species, (C) ceramide species, and (D) the relationship between insulin sensitivity and Cer18:0 levels in muscle. (E) Total lipid levels, (F) DAG …

Figure 6—figure supplement 1
Levels of sphingomyelin (SM), phosphatidylcholine (PC), phosphatidylethanolamine (PE), or phosphatidylserine (PS) in muscle.

Grey – chow, blue – high starch (Hi-ST), pink – high fat (Hi-F). Data presented as mean ± SEM. Data analysed with a Kruskal-Wallis test with pairwise Wilcoxon rank sum used for post hoc comparisons. …

Figure 6—figure supplement 2
Levels of sphingomyelin (SM), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and cholesterol esters (CE) in liver.

Grey – chow, blue – high starch (Hi-ST), pink – high fat (Hi-F). Data presented as mean ± SEM. Data analysed with a Kruskal-Wallis test with pairwise Wilcoxon rank sum used for post hoc comparisons. …

Tables

Table 1
Enzyme activities in liver and muscle.
Enzyme activityμmol/min/g proteinChowHi-STHi-F
Liver
 Citrate synthase110.8±7.3140.1±3.0*119.9±6.1
 βHAD100.4±5.2117.0±2.1122.7±7.0*
 Succinate dehydrogenase14.1±0.615.1±0.415.1±1.2
 Pyruvate dehydrogenase0.90±0.210.73±0.330.36±0.07
Quadriceps muscle
 Citrate synthase188.7±5.1208.0±6.0*223.1±3.7*
 βHAD23.9±1.228.4±1.4*35.4±1.2*#
 Succinate dehydrogenase2.7±0.12.7±0.12.5±0.2
 Pyruvate dehydrogenase0.46±0.080.33±0.100.15±0.04*
  1. Data expressed as mean ± SEM. n=7–10. *p<0.05 compared to chow; #p<0.05 compared to Hi-ST.

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