Non-shivering thermogenesis is found in tissues other than brown adipose tissue during cold exposure. By: Jessica Chan & Dayna Weststeyn

Transcription

1 Non-shivering thermogenesis is found in tissues other than brown adipose tissue during cold exposure By: Jessica Chan & Dayna Weststeyn

2 Hypothesis The hypothesis for this point presentation is that non-shivering thermogenesis is found in tissues other than brown adipose tissue during cold exposure. The hypothesis for this counterpoint is that nonshivering thermogenesis during cold exposure is not found in tissues other than brown adipose tissue.

3 Research Supporting our Hypothesis Non-shivering thermogenesis on cold exposure occurs in skeletal muscle1

4 Experiment Methods: Respiration chambers 1 Baseline and cold exposure 1 High resolution respirometry 1 Mitochondrial uncoupling 1 Muscle Biopsies 1 Oxygen consumption 1 Subject Information 1 : -11 Subjects -Height: 184± 3 cm -Body mass: 77.7±2.7 kg BMI: 22.9±0.6 kg/m2 Age: 21.7±0.6 years -Not using medication -Wearing standardized clothing -Equal macronutrient composition: 47% energy from carbohydrate, 38% from fat and 15% from protein No shivering was reported by subjects Study by: Wijers SL, Schrauwen P, Saris WH, van Marken Lichtenbelt, 2008

5 Experiment Results: Figure 1: Wijers SL, Schrauwen P, Saris WH, van Marken Lichtenbelt, 2008

6 Experiment Results: Figure 2: Wijers SL, Schrauwen P, Saris WH, van Marken Lichtenbelt, 2008

7 T3 Previous studies have shown mitochondrial uncoupling in skeletal muscle can be stimulated by Triiodothyronine (T3) infusion 1

8 Ancestry Progenitor cells for brown adipose tissue have been discovered in skeletal muscle 2 Skeletal muscle and brown adipose tissue cells may develop from a similar ancestry 2

9 Experiment: PET Scanning Study by: Ouellet et al., 2008 tested glucose and NEFA uptake in various tissues PET scanning 18 F-fluorodeoxyglucosue (FDG) for glucose 18 F-fluoro-thiaheptadecanoic acid (FTHA) for nonesterified fatty acid uptake (NEFA)

10 Figure 3: Ouellet et al., 2008

11 Results Figure 4: Ouellet et al., 2008

12 Heat Production Total heat production of activated BAT = ~ 55W/Kg, which equals roughly 4.5% basal metabolic rate BMR 3 NST contributes up to 15% of the resting metabolic rate (RMR) 3 Lichtenbelt and Schrauwen (2011) Image, clip art,

13 UCP-1 ablated mice do not cease shivering upon cold exposure4,5 Image (left): Mouse strain database, author unknown, Image (right): Mouse Strain Datasheet, author unknown

14 Drawbacks/ Limitations Parallels to humans 4 Flanking regions in close proximity to the ablation sites in mice 6 Difficult to make definite conclusions 6 C57/B16 & 129-strain mice

15 Limitations: Norepinephrine injection Overestimation of the capacity for non-shivering thermogenesis from UCP-17 Image: Norepinephrine structure, author unknown,

16 Limitations: PET/CT Scanning PET /CT Scanners 18cm long 8 Deeper areas harder to assess 8

17 Cold Stay: Intermittent vs. Continuous Intermittent, short duration cold stay experiments show that skeletal muscle state 4 respiration did not increase 9 Continuous, longer cold stay experiments show that skeletal muscle state 4 respiration does increase 1, 9

18 Conclusion In conclusion, the evidence presented supports our hypothesis that non-shivering thermogenesis is involved in tissues other than brown adipose tissue.

19 References References: 1. Wijers SL, Schrauwen P, Saris WH, van Marken Lichtenbelt WD. Human skeletal muscle mitochondrial uncoupling is associated with cold induced adaptive thermogenesis. PLoS One. Vol 3, No. 3, pg. 1-5, Timmons, JA., Wennmalm, K., Larsson, O., Walden, TB., Lassmann, T., Petrovic, N., Hamilton, DL, Gimeno, RE, Wahlestedt, C., Baar, K., Nedergaard, J., Cannon, B.Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. : National Academy of Sciences: Vol. 104, No.11, pg van Marken Lichtenbelt WD, Schrauwen P. Implications of nonshivering thermogenesis for energy balance regulation in humans. Am J Physiol Regul Integr Comp Physiol. Vol 301, No. 2, pg. R Cannon B, Nedergaard J. Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans). National Center for Biotechnology Information. Vol. 34, pg. 7-17, Golozoubova, V., Hohtola, E., Matthias, A., Jacobsson, A., Cannon, B., Nedergaard, J.Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold. The Official Journal of the Federation of American Societies for Experimental Biology. Vol. 15, No.11, pg , Eisener-Dorman AF, Lawrence DA, Bolivar VJ. Cautionary Insights on Knockout Mouse Studies: The Gene or Not the Gene? Brain, behavior, and immunity. Vol. 23, No.3, pg Cannon, B. & Nedergaard, J. Nonshivering thermogenesis and its adequate measurement in metabolic studies. The Journalof Experimental Biology. Volume 214, pg Ouellet V, Labbe SM, Blondin DP, et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest. 2012;122(2): Van der Lans AA, Hoeks J, Brans B, et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest. 2013;123(8):