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Q5 - UCP Family and Non-Shivering Thermogenesis

Theoretical A Real exam question - full text reproduced under IBO's CC BY-NC-SA 4.0 license
Comparative Thermoregulation

One way of heat production is non-shivering thermogenesis, mediated by norepinephrine via upregulation of mitochondrial uncoupling channel proteins (UCP) in brown adipose tissue (BAT). UCP increases the H⁺ conductance of the inner mitochondrial membrane to dissipate the mitochondrial H⁺ gradient and convert the energy of substrate oxidation into heat. To identify the member(s) of the UCP family responsible for the process, we carried out two experiments.

Figure 1 compares relative effects of acclimation to a cool environment for mice (from thermoneutrality at 30°C to the relative cold of 18°C) on the mRNA levels of different members of the uncoupling protein family in BAT.

Line graph: UCP1, UCP2 and UCP3 mRNA (% of 30°C level) at acclimation temperatures 18°C, 24°C and 30°C. UCP1 is highest overall and rises steeply from ~100 (at 30°C) to ~1700 (at 18°C). UCP3 rises more modestly, from ~100 to ~700. UCP2 stays low and flat throughout. Fig.1. Axis 1 = Acclimation temperature (°C). Axis 2 = % of 30°C level.

In a following experiment, three transgenic mouse strains were generated, bearing a single knock out mutation of either UCP1 or UCP3 and another bearing knock out mutations of both UCP1 and UCP3. We then measured metabolic rate in warm acclimated (30°C) and cool acclimated (18°C) conditions. In each case, besides the basal metabolic rate, we also measured metabolic rate following the injection of norepinephrine (NE).

Bar chart, four groups (normal, UCP1-KO, UCP3-KO, UCP1+UCP3 double-KO mice) × warm/cool acclimation × ± NE. Normal mice: warm 7.5→15 with NE, cool 10→26 with NE. UCP1-KO: warm 7.5→12, cool 10→15. UCP3-KO: warm 6→13, cool 8→24. Double-KO: warm 7.5→12, cool 10→15. Fig.2. Axis = Metabolic rate (ml O₂·min⁻¹·kg⁻¹). Title 1 = Normal mice. Title 2 = UCP1-knockout mice. Title 3 = UCP3-knockout mice. Title 4 = UCP3-UCP1-double knockout mice. Legend 1 = Warm-acclimated. Legend 2 = Cool-acclimated.

Q5.1. Estimate the increase in metabolic rate due to UCP1-dependent thermogenesis after NE stimulation in cool-acclimated mice (in ml O2·min⁻¹·kg⁻¹).
Q5.2. Calculate the increase in O2 consumption in a 25-gram cool-acclimated mouse that results from NE stimulation but cannot be explained by UCP1 or UCP3 activity (in ml·min⁻¹).
Q5.3. UCP1 actively pumps H+ ions across the inner mitochondrial membrane.
Q5.4. The results from this experiment suggest that UCP1 is the most important UCP for non-shivering thermogenesis in response to cold.
Q5.5. Patients taking DNP experience hypothermia as their cells are not able to generate energy.
Q5.6. A patient with mild DNP overdose can be treated by glucose administration.
Q5.7. Mitochondrial uncoupling occurs under certain physiological conditions in animals.
Q5.8. DNP reduces the oxygen consumption of cells.
Q5.9. DNP increases the pH in the mitochondrial intermembrane space.
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Question reproduced from IBO 2019, Theoretical Exam A, licensed under CC BY-NC-SA 4.0 - attributed to the International Biology Olympiad. Open the full exam PDF · Official answer key