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Energy flow and metabolic efficiency attributed to brown adipose tissue
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. (Nedergaard)
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The large capacity of brown adipose tissue (BAT) to expend energy as heat makes it an interesting potential player in weight regulation and other metabolic conditions. This is of particular interest as it has been recognized that adult humans possess BAT. The protein responsible for the heat production is uncoupling protein 1 (UCP1), which, as the name implies, uncouples the respiratory chain from ATP production; instead heat is produced. Cold is the strongest recruiter and activator of BAT. However, also obesogenic food has a low but nonetheless significant effect on the recruitment and activation of UCP1, although the significance of this has been discussed.

In the present thesis, I have studied the effect of diet on BAT and the possibilities for it to be obesity-protective. This can be done by comparing responses in wild-type mice and in UCP1-ablated mice. Since the effect of diet on BAT is low, it is of importance to control the temperature and maintain thermoneutrality. Other confounding factors to keep in mind are differences in actual energy and composition of food and also cohort differences. When controlling all the parameters mentioned and giving the mice the same obesogenic diet, the mice possessing UCP1 compared to UCP1-ablated mice had higher energy expenditure, and lower weight gain, despite eating more. This confirms the presence of a UCP1-dependent diet-induced thermogenesis. Thus, the conclusion must be that possessing UCP1 does result in obesity protection at thermoneutrality. However, the relevance for human energy balance is still not established.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , 2017. , p. 86
Keywords [en]
Brown adipose tissue, BAT, UCP1, diet-induced thermogenesis, DIT, obesity, high-fat diet, energy expenditure
National Category
Physiology
Research subject
Physiology
Identifiers
URN: urn:nbn:se:su:diva-140190ISBN: 978-91-7649-734-0 (print)ISBN: 978-91-7649-735-7 (electronic)OAI: oai:DiVA.org:su-140190DiVA, id: diva2:1079001
Public defence
2017-04-07, Vivi Täckholmsalen (Q-salen), NPQ-huset, Svante Arrhenius väg 20, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 2: Manuscript. Paper 3: Manuscript.

Available from: 2017-03-15 Created: 2017-03-07 Last updated: 2018-01-13Bibliographically approved
List of papers
1. Adaptive Facultative Diet-induced Thermogenesis in Wild-type but not in UCP1-ablated Mice
Open this publication in new window or tab >>Adaptive Facultative Diet-induced Thermogenesis in Wild-type but not in UCP1-ablated Mice
(English)Manuscript (preprint) (Other academic)
Keywords
Brown adipose tissue, facultative diet-induced thermogenesis, energy expenditure, UCP1, uncoupling protein 1, oxygen consumption, UCP!-ablated, mice
National Category
Biological Sciences Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-140443 (URN)
Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2018-01-13Bibliographically approved
2. Highly recruited brown adipose tissue does not in itself protect against obesity
Open this publication in new window or tab >>Highly recruited brown adipose tissue does not in itself protect against obesity
Show others...
(English)Manuscript (preprint) (Other academic)
Keywords
Brown adipose tissue, UCP1, uncoupling protein 1, UCP!-ablated, mice, cold-recruited, thermoneutrality, high-fat diet, body fat
National Category
Biological Sciences Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-140444 (URN)
Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2018-01-13Bibliographically approved
3. At thermoneutrality, medium-chain fatty acids totally protect against diet-induced obesity in a UCP1-independent manner
Open this publication in new window or tab >>At thermoneutrality, medium-chain fatty acids totally protect against diet-induced obesity in a UCP1-independent manner
(English)Manuscript (preprint) (Other academic)
Keywords
Brown adipose tissue, UCP1, uncoupling protein 1, UCP!-ablated, mice, thermoneutrality, high-fat diet, body fat, medium-chain triglycerides
National Category
Biological Sciences Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-140445 (URN)
Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2018-01-13Bibliographically approved
4. No insulating effect of obesity
Open this publication in new window or tab >>No insulating effect of obesity
Show others...
2016 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 311, no 1, p. e202-e213Article in journal (Refereed) Published
Abstract [en]

The development of obesity may be aggravated if obesity itself insulates against heat loss and thus diminishes the amount of food burnt for body temperature control. This would be particularly important under normal laboratory conditions where mice experience a chronic cold stress (at approximate to 20 degrees C). We used Scholander plots (energy expenditure plotted against ambient temperature) to examine the insulation (thermal conductance) of mice, defined as the inverse of the slope of the Scholander curve at subthermoneutral temperatures. We verified the method by demonstrating that shaved mice possessed only half the insulation of non-shaved mice. We examined a series of obesity models [mice fed high-fat diets and kept at different temperatures, classical diet-induced obese mice, ob/ob mice, and obesity-prone (C57BL/6) vs. obesity-resistant (129S)mice]. We found that neither acclimation temperature nor any kind or degree of obesity affected the thermal insulation of the mice when analyzed at the whole mouse level or as energy expenditure per lean weight. Calculation per body weight erroneously implied increased insulation in obese mice. We conclude that, in contrast to what would be expected, obesity of any kind does not increase thermal insulation in mice, and therefore, it does not in itself aggravate the development of obesity. It may be discussed as to what degree of effect excess adipose tissue has on insulation in humans and especially whether significant metabolic effects are associated with insulation in humans.

Keywords
obesity, insulation, ob/ob
National Category
Biological Sciences Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-133223 (URN)10.1152/ajpendo.00093.2016 (DOI)000380372000016 ()27189935 (PubMedID)
Available from: 2016-09-13 Created: 2016-09-05 Last updated: 2018-01-10Bibliographically approved

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