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Repeated short excursions from thermoneutrality suffice to restructure brown adipose tissue
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0002-4435-9651
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0001-6594-2363
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2023 (English)In: Biochimie, ISSN 0300-9084, E-ISSN 1638-6183, Vol. 210, p. 40-49Article in journal (Refereed) Published
Abstract [en]

Given the presence of brown adipose tissue in adult humans, an important issue is whether human brown adipose tissue is recruitable. Cold exposure is the canonical recruitment treatment; however, in experimental animals (mice), recruitment of brown adipose tissue is normally induced by placing the mice in constant cold, a procedure not feasible in humans. For possible translational applications, we have therefore investigated whether shorter daily excursions from thermoneutrality would suffice to qualitatively and quantitatively induce recruitment in mice. Mice, housed at thermoneutrality (30 °C) to mimic human conditions, were transferred every day for 4 weeks to cool conditions (18 °C), for 0, 15, 30, 120 and 420 min (or placed constantly in 18 °C). On the examination day, the mice were not exposed to cold. Very short daily exposures (≤30 minutes) were sufficient to induce structural changes in the form of higher protein density in brown adipose tissue, changes that may affect the identification of the tissue in e.g. computer tomography and other scan studies. To estimate thermogenic capacity, UCP1 protein levels were followed. No UCP1 protein was detectable in inguinal white adipose tissue. In the interscapular brown adipose tissue, a remarkable two-phase reaction was seen. Very short daily exposures (≤30 minutes) were sufficient to induce a significant increase in total UCP1 levels. For attainment of full cold acclimation, the mice had, however, to remain exposed to the cold. The studies indicate that marked alterations in brown adipose tissue composition can be induced in mammals through relatively modest stimulation events.

Place, publisher, year, edition, pages
2023. Vol. 210, p. 40-49
National Category
Medical Bioscience
Identifiers
URN: urn:nbn:se:su:diva-214074DOI: 10.1016/j.biochi.2023.01.006PubMedID: 36657658Scopus ID: 2-s2.0-85148701823OAI: oai:DiVA.org:su-214074DiVA, id: diva2:1729898
Available from: 2023-01-23 Created: 2023-01-23 Last updated: 2023-10-12Bibliographically approved
In thesis
1. Dietary, Pharmacological and Environmental Effects on Brown Adipose Tissue
Open this publication in new window or tab >>Dietary, Pharmacological and Environmental Effects on Brown Adipose Tissue
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity is a common health issue; over 12 % of the adult world population have obesity. Obesity has many co-morbidities including cardo-vascular diseases and diabetes. Obesity is the result of chronic positive energy balance, eating too much and expending too little. There are several drugs on the market for treating obesity, but they have limited efficiency and have thus far been unable to halt the current obesity epidemic. All current obesity drugs function by reducing food intake, which is only one half of the energy balance equation, the other being energy expenditure.

The measurement of heat exchange, calorimetry, has a long history, stretching back to the late 18th century. Today most calorimetry on animals uses an indirect method, measuring oxygen consumption and carbon dioxide production. These machines are generally termed respirometers or indirect calorimeters. Already in the late 19th century, it was shown that direct and indirect calorimetry have very close agreement. In animal metabolism carbohydrates, fat and protein, together with oxygen, go through many enzymatic processes, finally resulting in mainly carbon dioxide, water, urea and adenosine triphosphate (ATP). Brown adipose tissue (BAT) can uncouple this process from the final step, ATP production, using the mitochondrial protein uncoupling protein 1 (UCP1), yielding heat.

BAT is a heat-producing organ in many mammals, including humans. Active BAT in adult humans was re-discovered in a metabolic context relatively recently, in 2007, which increased the interest in this field markedly. When activated, BAT has very high energy expenditure per tissue weight. There are currently no safe and comfortable ways to induce BAT recruitment and activation, potentially except for short exposure to moderate cold (II). It is hoped that BAT recruitment and activation may be utilised, in the future, to increase energy expenditure and be used to treat obesity.

In this thesis, I have investigated thyroxine (IV), noradrenaline and a beta-3 selective agonist, CL 316,243 (I). I found that thyroxine recruits BAT, but thyroxine can raise energy expenditure in UCP1-knockout (UCP1-KO) mice as well. I also found that noradrenaline and CL 316,243 both activated BAT, with noradrenaline being slightly more efficient, and injections of these drugs could be used to measure maximum BAT activity in vivo utilising respirometry. I have also determined that as little as 15-minute exposure per day to moderate cold could significantly recruit UCP1 (II).

Diets can also impact BAT. I have investigated the effects of diets high in fat and sugar (HFD) (III; V) on BAT. I found that mice fed these diets increased energy expenditure, especially during mealtime, in a UCP1-dependent manner. Finally, I found that highly recruited UCP1 did not protect against obesity when not activated. Mice with highly recruited, but non-active, UCP1 even transiently gained more weight than mice with non-recruited UCP1.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2023. p. 125
Keywords
Obesity, brown adipose tissue, uncoupling protein 1, moderate cold exposure, calorimetry, thyroxine, dietary protein, thermic effect of food, diet-induced thermogenesis, adrenergic stimulation, mice, physiology
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Bioscience
Identifiers
urn:nbn:se:su:diva-214080 (URN)978-91-8014-172-7 (ISBN)978-91-8014-173-4 (ISBN)
Public defence
2023-03-17, Vivi Täckholmsalen (Q-salen), NPQ-huset, Svante Arrhenius väg 20, STOCKHOLM, 10:00 (English)
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Available from: 2023-02-27 Created: 2023-01-23 Last updated: 2023-02-27Bibliographically approved

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Davies, Victoria S.Lindsund, ErikPetrovic, NatasaCannon, BarbaraNedergaard, Jan

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