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Kalinovich, Anastasia
Alternative names
Publications (10 of 16) Show all publications
Shabalina, I., Edgar, D., Gibanova, N., Kalinovich, A., Petrovic, N., Vyssokikh, M. Y., . . . Nedergaard, J. (2024). Enhanced ROS Production in Mitochondria from Prematurely Aging mtDNA Mutator Mice. Biochemistry (Moscow), 89(2), 279-298
Open this publication in new window or tab >>Enhanced ROS Production in Mitochondria from Prematurely Aging mtDNA Mutator Mice
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2024 (English)In: Biochemistry (Moscow), ISSN 0006-2979, E-ISSN 1608-3040, Vol. 89, no 2, p. 279-298Article in journal (Refereed) Published
Abstract [en]

An increase in mitochondrial DNA (mtDNA) mutations and an ensuing increase in mitochondrial reactive oxygen species (ROS) production have been suggested to be a cause of the aging process (the mitochondrial hypothesis of aging). In agreement with this, mtDNA-mutator mice accumulate a large amount of mtDNA mutations, giving rise to defective mitochondria and an accelerated aging phenotype. However, incongruously, the rates of ROS production in mtDNA mutator mitochondria have generally earlier been reported to be lower - not higher - than in wildtype, thus apparently invalidating the mitochondrial hypothesis of aging. We have here re-examined ROS production rates in mtDNA-mutator mice mitochondria. Using traditional conditions for measuring ROS (succinate in the absence of rotenone), we indeed found lower ROS in the mtDNA-mutator mitochondria compared to wildtype. This ROS mainly results from reverse electron flow driven by the membrane potential, but the membrane potential reached in the isolated mtDNA-mutator mitochondria was 33 mV lower than that in wildtype mitochondria, due to the feedback inhibition of succinate oxidation by oxaloacetate, and to a lower oxidative capacity in the mtDNA-mutator mice, explaining the lower ROS production. In contrast, in normal forward electron flow systems (pyruvate (or glutamate) + malate or palmitoyl-CoA + carnitine), mitochondrial ROS production was higher in the mtDNA-mutator mitochondria. Particularly, even during active oxidative phosphorylation (as would be ongoing physiologically), higher ROS rates were seen in the mtDNA-mutator mitochondria than in wildtype. Thus, when examined under physiological conditions, mitochondrial ROS production rates are indeed increased in mtDNA-mutator mitochondria. While this does not prove the validity of the mitochondrial hypothesis of aging, it may no longer be said to be negated in this respect. This paper is dedicated to the memory of Professor Vladimir P. Skulachev.

Keywords
mtDNA mutator mice, ROS production, aging, succinate, membrane potential, oxidative phosphorylation
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-228605 (URN)10.1134/S0006297924020081 (DOI)001190797800013 ()38622096 (PubMedID)2-s2.0-85188236462 (Scopus ID)
Available from: 2024-04-23 Created: 2024-04-23 Last updated: 2024-04-23Bibliographically approved
Gómez Rodríguez, A., Talamonti, E., Naudi, A., Kalinovich, A. V., Pauter, A. M., Barja, G., . . . Shabalina, I. G. (2022). Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria. Nutrients, 14(3), Article ID 559.
Open this publication in new window or tab >>Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria
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2022 (English)In: Nutrients, E-ISSN 2072-6643, Vol. 14, no 3, article id 559Article in journal (Refereed) Published
Abstract [en]

The fatty acid elongase elongation of very long-chain fatty acids protein 2 (ELOVL2) controls the elongation of polyunsaturated fatty acids (PUFA) producing precursors for omega-3, docosahexaenoic acid (DHA), and omega-6, docosapentaenoic acid (DPAn-6) in vivo. Expectedly, Elovl2-ablation drastically reduced the DHA and DPAn-6 in liver mitochondrial membranes. Unexpectedly, however, total PUFAs levels decreased further than could be explained by Elovl2 ablation. The lipid peroxidation process was not involved in PUFAs reduction since malondialdehyde-lysine (MDAL) and other oxidative stress biomarkers were not enhanced. The content of mitochondrial respiratory chain proteins remained unchanged. Still, membrane remodeling was associated with the high voltage-dependent anion channel (VDAC) and adenine nucleotide translocase 2 (ANT2), a possible reflection of the increased demand on phospholipid transport to the mitochondria. Mitochondrial function was impaired despite preserved content of the respiratory chain proteins and the absence of oxidative damage. Oligomycin-insensitive oxygen consumption increased, and coefficients of respiratory control were reduced by 50%. The mitochondria became very sensitive to fatty acid-induced uncoupling and permeabilization, where ANT2 is involved. Mitochondrial volume and number of peroxisomes increased as revealed by transmission electron microscopy. In conclusion, the results imply that endogenous DHA production is vital for the normal function of mouse liver mitochondria and could be relevant not only for mice but also for human metabolism.

Keywords
docosahexaenoic acid (DHA) deficiency, mitochondrial function, polyunsaturated fatty acids, membrane permeabilization, oxidative damage markers, adenine nucleotide translocase
National Category
Health Sciences
Identifiers
urn:nbn:se:su:diva-202398 (URN)10.3390/nu14030559 (DOI)000754768000001 ()
Available from: 2022-02-24 Created: 2022-02-24 Last updated: 2023-08-28Bibliographically approved
van Beek, S. M. M., Kalinovich, A., Schaart, G., Bengtsson, T. & Hoeks, J. (2021). Prolonged b(2)-adrenergic agonist treatment improves glucose homeostasis in diet-induced obese UCP1(-/-) mice. American Journal of Physiology. Endocrinology and Metabolism, 320(3), E619-E628
Open this publication in new window or tab >>Prolonged b(2)-adrenergic agonist treatment improves glucose homeostasis in diet-induced obese UCP1(-/-) mice
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2021 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 320, no 3, p. E619-E628Article in journal (Refereed) Published
Abstract [en]

Prolonged supplementation with the b2-agonist clenbuterol improves glucose homeostasis in diabetic rodents, likely via b2-adreno-ceptor (b2-AR)-mediated effects in the skeletal muscle and liver. However, since rodents have, in contrast to—especially diabetic—humans, substantial quantities of brown adipose tissue (BAT) and clenbuterol has affinity to b1- and b3-ARs, the contribution of BAT tothese improvements is unclear. Therefore, we investigated clenbuterol-mediated improvements in glucose homeostasis in uncouplingprotein 1-deficient (UCP1/) mice, lacking thermogenic BAT, versus wild-type (WT) mice. Anesthetized WT and UCP1/C57Bl/6 micewere injected with saline or clenbuterol and whole body oxygen consumption was measured. Furthermore, male WT and UCP1/C57Bl/6 mice were subjected to 17-wk of chow feeding, high-fat feeding, or high-fat feeding with clenbuterol treatment betweenweeks 13 and 17. Body composition was measured weekly with MRI. Oral glucose tolerance and insulin tolerance tests were per-formed in week 15 and 17, respectively. Clenbuterol increased oxygen consumption approximately twofold in WT mice. This increasewas blunted in UCP1/mice, indicating clenbuterol-mediated activation of BAT thermogenesis. High-fat feeding induced diabeto-genic phenotypes in both genotypes. However, low-dose clenbuterol treatment for 2 wk significantly reduced fasting blood glucoseby 12.9% in WT and 14.8% in UCP1/mice. Clenbuterol treatment improved glucose and insulin tolerance in both genotypes com-pared with HFD controls and normalized to chow-fed control mice independent of body mass and composition alterations.Clenbuterol improved whole body glucose homeostasis independent of UCP1. Given the low human abundancy of BAT, b2-AR ago-nist treatment provides a potential novel route for glucose disposal in diabetic humans.

Keywords
b2-adrenergic agonist, brown adipose tissue, skeletal muscle, type 2 diabetes mellitus, UCP1
National Category
Endocrinology and Diabetes Physiology
Identifiers
urn:nbn:se:su:diva-194545 (URN)10.1152/ajpendo.00324.2020 (DOI)000643493300014 ()33522400 (PubMedID)
Available from: 2021-08-03 Created: 2021-08-03 Last updated: 2022-02-25Bibliographically approved
Dehvari, N., Sato, M., Bokhari, M. H., Kalinovich, A., Ham, S., Gao, J., . . . Hutchinson, D. S. (2020). The metabolic effects of mirabegron are mediated primarily by beta(3)-adrenoceptors. Pharmacology Research & Perspectives, 8(5), Article ID e00643.
Open this publication in new window or tab >>The metabolic effects of mirabegron are mediated primarily by beta(3)-adrenoceptors
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2020 (English)In: Pharmacology Research & Perspectives, E-ISSN 2052-1707, Vol. 8, no 5, article id e00643Article in journal (Refereed) Published
Abstract [en]

The beta(3)-adrenoceptor agonist mirabegron is approved for use for overactive bladder and has been purported to be useful in the treatment of obesity-related metabolic diseases in humans, including those involving disturbances of glucose homeostasis. We investigated the effect of mirabegron on glucose homeostasis with in vitro and in vivo models, focusing on its selectivity at beta-adrenoceptors, ability to cause browning of white adipocytes, and the role of UCP1 in glucose homeostasis. In mouse brown, white, and brite adipocytes, mirabegron-mediated effects were examined on cyclic AMP, UCP1 mRNA, [H-3]-2-deoxyglucose uptake, cellular glycolysis, and O(2)consumption. Mirabegron increased cyclic AMP levels, UCP1 mRNA content, glucose uptake, and cellular glycolysis in brown adipocytes, and these effects were either absent or reduced in white adipocytes. In brite adipocytes, mirabegron increased cyclic AMP levels and UCP1 mRNA content resulting in increased UCP1-mediated oxygen consumption, glucose uptake, and cellular glycolysis. The metabolic effects of mirabegron in both brown and brite adipocytes were primarily due to actions at beta(3)-adrenoceptors as they were largely absent in adipocytes derived from beta(3)-adrenoceptor knockout mice. In vivo, mirabegron increased whole body oxygen consumption, glucose uptake into brown and inguinal white adipose tissue, and improved glucose tolerance, all effects that required the presence of the beta(3)-adrenoceptor. Furthermore, in UCP1 knockout mice, the effects of mirabegron on glucose tolerance were attenuated. Thus, mirabegron had effects on cellular metabolism in adipocytes that improved glucose handling in vivo, and were primarily due to actions at the beta(3)-adrenoceptor.

Keywords
adipocyte, glucose, mirabegron, UCP1, beta(3)-adrenoceptor
National Category
Physiology
Identifiers
urn:nbn:se:su:diva-187651 (URN)10.1002/prp2.643 (DOI)000578658700022 ()32813332 (PubMedID)
Available from: 2020-12-23 Created: 2020-12-23 Last updated: 2022-02-25Bibliographically approved
Kalinovich, A., Dehvari, N., Åslund, A., van Beek, S., Halleskog, C., Olsen, J., . . . Bengtsson, T. (2020). Treatment with a β-2-adrenoceptor agonist stimulates glucose uptake in skeletal muscle and improves glucose homeostasis, insulin resistance and hepatic steatosis in mice with diet-induced obesity. Diabetologia, 63(8), 1603-1615
Open this publication in new window or tab >>Treatment with a β-2-adrenoceptor agonist stimulates glucose uptake in skeletal muscle and improves glucose homeostasis, insulin resistance and hepatic steatosis in mice with diet-induced obesity
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2020 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, no 8, p. 1603-1615Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis Chronic stimulation of beta(2)-adrenoceptors, opposite to acute treatment, was reported to reduce blood glucose levels, as well as to improve glucose and insulin tolerance in rodent models of diabetes by essentially unknown mechanisms. We recently described a novel pathway that mediates glucose uptake in skeletal muscle cells via stimulation of beta(2)-adrenoceptors. In the current study we further explored the potential therapeutic relevance of beta(2)-adrenoceptor stimulation to improve glucose homeostasis and the mechanisms responsible for the effect.

Methods C57Bl/6N mice with diet-induced obesity were treated both acutely and for up to 42 days with a wide range of clenbuterol dosages and treatment durations. Glucose homeostasis was assessed by glucose tolerance test. We also measured in vivo glucose uptake in skeletal muscle, insulin sensitivity by insulin tolerance test, plasma insulin levels, hepatic lipids and glycogen.

Results Consistent with previous findings, acute clenbuterol administration increased blood glucose and insulin levels. However, already after 4 days of treatment, beneficial effects of clenbuterol were manifested in glucose homeostasis (32% improvement of glucose tolerance after 4 days of treatment,p < 0.01) and these effects persisted up to 42 days of treatment. These favourable metabolic effects could be achieved with doses as low as 0.025 mg kg(-1) day(-1)(40 times lower than previously studied). Mechanistically, these effects were not due to increased insulin levels, but clenbuterol enhanced glucose uptake in skeletal muscle in vivo both acutely in lean mice (by 64%,p < 0.001) as well as during chronic treatment in diet-induced obese mice (by 74%,p < 0.001). Notably, prolonged treatment with low-dose clenbuterol improved whole-body insulin sensitivity (glucose disposal rate after insulin injection increased up to 1.38 +/- 0.31%/min in comparison with 0.15 +/- 0.36%/min in control mice,p < 0.05) and drastically reduced hepatic steatosis (by 40%,p < 0.01) and glycogen (by 23%,p < 0.05).

Conclusions/interpretation Clenbuterol improved glucose tolerance after 4 days of treatment and these effects were maintained for up to 42 days. Effects were achieved with doses in a clinically relevant microgram range. Mechanistically, prolonged treatment with a low dose of clenbuterol improved glucose homeostasis in insulin resistant mice, most likely by stimulating glucose uptake in skeletal muscle and improving whole-body insulin sensitivity as well as by reducing hepatic lipids and glycogen. We conclude that selective beta(2)-adrenergic agonists might be an attractive potential treatment for type 2 diabetes. This remains to be confirmed in humans.

Keywords
beta(2)-Adrenergic signalling, Clenbuterol, Hepatic steatosis, Insulin resistance, Skeletal muscle, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:su:diva-184358 (URN)10.1007/s00125-020-05171-y (DOI)000546959500015 ()32472192 (PubMedID)
Available from: 2020-10-06 Created: 2020-10-06 Last updated: 2022-02-25Bibliographically approved
Fischer, K., Ruiz, H. H., Jhun, K., Finan, B., Oberlin, D. J., van der Heide, V., . . . Buettner, C. (2017). Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nature Medicine, 23(5), 623-630
Open this publication in new window or tab >>Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis
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2017 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 23, no 5, p. 623-630Article in journal (Refereed) Published
Abstract [en]

Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through beta 3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1(-/-) and interleukin-4 receptor-alpha double-negative (Il4ra(-/-)) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-143404 (URN)10.1038/nm.4316 (DOI)000400650700017 ()28414329 (PubMedID)
Available from: 2017-05-29 Created: 2017-05-29 Last updated: 2022-02-28Bibliographically approved
Kalinovich, A. V., de Jong, J. M. A., Cannon, B. & Nedergaard, J. (2017). UCP1 in adipose tissues: two steps to full browning. Biochimie, 134, 127-137
Open this publication in new window or tab >>UCP1 in adipose tissues: two steps to full browning
2017 (English)In: Biochimie, ISSN 0300-9084, E-ISSN 1638-6183, Vol. 134, p. 127-137Article in journal (Refereed) Published
Abstract [en]

The possibility that brown adipose tissue thermogenesis can be recruited in order to combat the development of obesity has led to a high interest in the identification of "browning agents", i.e. agents that increase the amount and activity of UCP1 in brown and brite/beige adipose tissues. However, functional analysis of the browning process yields confusingly different results when the analysis is performed in one of two alternative steps. Thus, in one of the steps, using cold acclimation as a potent model browning agent, we find that if the browning process is followed in mice initially housed at 21 °C (the most common procedure), there is only weak molecular evidence for increases in UCP1 gene expression or UCP1 protein abundance in classical brown adipose tissue; however, in brite/beige adipose depots, there are large increases, apparently associating functional browning with events only in the brite/beige tissues. Contrastingly, in another step, if the process is followed starting with mice initially housed at 30 °C (thermoneutrality for mice, thus similar to normal human conditions), large increases in UCP1 gene expression and UCP1 protein abundance are observed in the classical brown adipose tissue depots; there is then practically no observable UCP1 gene expression in brite/beige tissues. This apparent conundrum can be resolved when it is realized that the classical brown adipose tissue at 21 °C is already essentially fully differentiated and thus expands extensively through proliferation upon further browning induction, rather than by further enhancing cellular differentiation. When the limiting factor for thermogenesis, i.e. the total amount of UCP1 protein per depot, is analyzed, classical brown adipose tissue is by far the predominant site for the browning process, irrespective of which of the two steps is analyzed. There are to date no published data demonstrating that alternative browning agents would selectively promote brite/beige tissues versus classical brown tissue to a higher degree than does cold acclimation. Thus, to restrict investigations to examine adipose tissue depots where only a limited part of the adaptation process occurs (i.e. the brite/beige tissues) and to use initial conditions different from the thermoneutrality normally experienced by adult humans may seriously hamper the identification of therapeutically valid browning agents. The data presented here have therefore important implications for the analysis of the potential of browning agents and the nature of human brown adipose tissue.

Keywords
Beige, Brite, Browning, Cold acclimation, UCP1
National Category
Cell Biology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-140881 (URN)10.1016/j.biochi.2017.01.007 (DOI)000395217100016 ()28109720 (PubMedID)
Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2022-03-23Bibliographically approved
Shabalina, I. G., Kalinovich, A. V., Cannon, B. & Nedergaard, J. (2016). Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria. Archives of Toxicology, 90(5), 1117-1128
Open this publication in new window or tab >>Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria
2016 (English)In: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 90, no 5, p. 1117-1128Article in journal (Refereed) Published
Abstract [en]

The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged.

Keywords
Uncoupling protein 1, Brown adipose tissue mitochondria, Environmental pollution, Reactive oxygen species, Membrane potential, Mitochondrial permeabilization
National Category
Biochemistry and Molecular Biology Pharmacology and Toxicology
Identifiers
urn:nbn:se:su:diva-131537 (URN)10.1007/s00204-015-1535-4 (DOI)000374303400008 ()26041126 (PubMedID)
Available from: 2016-07-01 Created: 2016-06-21 Last updated: 2022-03-23Bibliographically approved
Kalinovich, A. V., Mattsson, C. L., Youssef, M. R., Petrovic, N., Ost, M., Skulachev, V. P. & Shabalina, I. G. (2016). Mitochondria-targeted dodecyltriphenylphosphonium (C12TPP) combats high-fat-diet-induced obesity in mice. International Journal of Obesity, 40(12), 1864-1874
Open this publication in new window or tab >>Mitochondria-targeted dodecyltriphenylphosphonium (C12TPP) combats high-fat-diet-induced obesity in mice
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2016 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 12, p. 1864-1874Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A membrane-penetrating cation, dodecyltriphenylphosphonium (C12TPP), facilitates the recycling of fatty acids in the artificial lipid membrane and mitochondria. C12TPP can dissipate mitochondrial membrane potential and may affect total energy expenditure and body weight in animals and humans. METHODS: We investigated the metabolic effects of C12TPP in isolated brown-fat mitochondria, brown adipocyte cultures and mice in vivo. Experimental approaches included the measurement of oxygen consumption, carbon dioxide production, western blotting, magnetic resonance imaging and bomb calorimetry. RESULTS: In mice, C12TPP (50 mu mol per (day.kg body weight)) in the drinking water significantly reduced body weight (12%, P<0.001) and body fat mass (24%, P<0.001) during the first 7 days of treatment. C12TPP did not affect water palatability and intake or the energy and lipid content in feces. The addition of C12TPP to isolated brown-fat mitochondria resulted in increased oxygen consumption. Three hours of pretreatment with C12TPP also increased oligomycin-insensitive oxygen consumption in brown adipocyte cultures (P<0.01). The effects of C12TPP on mitochondria, cells and mice were independent of uncoupling protein 1 (UCP1). However, C12TPP treatment increased the mitochondrial protein levels in the brown adipose tissue of both wild-type and UCP1-knockout mice. Pair-feeding revealed that one-third of the body weight loss in C12TPP-treated mice was due to reduced food intake. C12TPP treatment elevated the resting metabolic rate (RMR) by up to 18% (P<0.05) compared with pair-fed animals. C12TPP reduced the respiratory exchange ratio, indicating enhanced fatty acid oxidation in mice. CONCLUSIONS: C12TPP combats diet-induced obesity by reducing food intake, increasing the RMR and enhancing fatty acid oxidation.

National Category
Biological Sciences Endocrinology and Diabetes Nutrition and Dietetics
Identifiers
urn:nbn:se:su:diva-139452 (URN)10.1038/ijo.2016.146 (DOI)000390680000007 ()27534841 (PubMedID)
Available from: 2017-02-22 Created: 2017-02-22 Last updated: 2022-03-23Bibliographically approved
Hilse, K. E., Kalinovich, A. V., Rupprecht, A., Smorodchenko, A., Zeitz, U., Staniek, K., . . . Pohl, E. E. (2016). The expression of UCP3 directly correlates to UCP1 abundance in brown adipose tissue. Biochimica et Biophysica Acta - Bioenergetics, 1857(1), 72-78
Open this publication in new window or tab >>The expression of UCP3 directly correlates to UCP1 abundance in brown adipose tissue
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2016 (English)In: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1857, no 1, p. 72-78Article in journal (Refereed) Published
Abstract [en]

UCP1 and UCP3 are members of the uncoupling protein (UCP) subfamily and are localized in the inner mitochondrial membrane. Whereas UCP1's central role in non-shivering thermogenesis is acknowledged, the function and even tissue expression pattern of UCP3 are still under dispute. Because UCP3 properties regarding transport of protons are qualitatively identical to those of UCP1, its expression in brown adipose tissue (BAT) alongside UCP1 requires justification. In this work, we tested whether any correlation exists between the expression of UCP1 and UCP3 in BAT by quantification of protein amounts in mouse tissues at physiological conditions, in cold-acclimated and UCP1 knockout mice. Quantification using recombinant UCP3 revealed that the UCP3 amount in BAT (0.51 ng/(mu g total tissue protein)) was nearly one order of magnitude higher than that in muscles and heart. Cold-acclimated mice showed an approximate three-fold increase in UCP3 abundance in BAT in comparison to mice in thermoneutral conditions. Surprisingly, we found a significant decrease of UCP3 in BAT of UCP1 knockout mice, whereas the protein amount in skeletal and heart muscles remained constant. UCP3 abundance decreased even more in cold-acclimated UCP1 knockout mice. Protein quantification in UCP3 knockout mice revealed no compensatory increase in UCP1 or UCP2 expression. Our results do not support the participation of UCP3 in thermogenesis in the absence of UCP1 in BAT, but clearly demonstrate the correlation in abundance between both proteins. The latter is important for understanding UCP3's function in BAT.

Keywords
Recombinant protein, Anti-UCP3 antibody, UCP3 knockout mice, Cold-acclimated mice, Skeletal muscles, Uncoupling protein 2
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-126189 (URN)10.1016/j.bbabio.2015.10.011 (DOI)000366771700008 ()
Available from: 2016-01-29 Created: 2016-01-26 Last updated: 2022-03-23Bibliographically approved
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