Caffeine exposure induces browning features in adipose tissue in vitro and in vivo. 2019

Ksenija Velickovic, and Declan Wayne, and Hilda Anaid Lugo Leija, and Ian Bloor, and David E Morris, and James Law, and Helen Budge, and Harold Sacks, and Michael E Symonds, and Virginie Sottile
Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), Division of Cancer & Stem Cells, University of Nottingham, Nottingham, NG7 2UH, United Kingdom.

Brown adipose tissue (BAT) is able to rapidly generate heat and metabolise macronutrients, such as glucose and lipids, through activation of mitochondrial uncoupling protein 1 (UCP1). Diet can modulate UCP1 function but the capacity of individual nutrients to promote the abundance and activity of UCP1 is not well established. Caffeine consumption has been associated with loss of body weight and increased energy expenditure, but whether it can activate UCP1 is unknown. This study examined the effect of caffeine on BAT thermogenesis in vitro and in vivo. Stem cell-derived adipocytes exposed to caffeine (1 mM) showed increased UCP1 protein abundance and cell metabolism with enhanced oxygen consumption and proton leak. These functional responses were associated with browning-like structural changes in mitochondrial and lipid droplet content. Caffeine also increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression and mitochondrial biogenesis, together with a number of BAT selective and beige gene markers. In vivo, drinking coffee (but not water) stimulated the temperature of the supraclavicular region, which co-locates to the main region of BAT in adult humans, and is indicative of thermogenesis. Taken together, these results demonstrate that caffeine can promote BAT function at thermoneutrality and may have the potential to be used therapeutically in adult humans.

UI MeSH Term Description Entries
D002001 Adipose Tissue, Brown A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids. Brown Fat,Hibernating Gland,Brown Adipose Tissue,Fat, Brown,Tissue, Brown Adipose
D002110 Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling. 1,3,7-Trimethylxanthine,Caffedrine,Coffeinum N,Coffeinum Purrum,Dexitac,Durvitan,No Doz,Percoffedrinol N,Percutaféine,Quick-Pep,Vivarin,Quick Pep,QuickPep
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000069796 Adipose Tissue, Beige Brown fat-like adipose tissue that develops in WHITE ADIPOSE TISSUE from non-MYOGENIC REGULATORY FACTOR 5 expressing cell lineage. Adipose Tissue, Brite,Beige Adipose Tissue,Beige Brite Adipose Tissue,Beige Brite Fat,Beige Fat,Brite Adipose Tissue,Brite Fat,Adipose Tissues, Beige,Adipose Tissues, Brite,Beige Adipose Tissues,Beige Brite Fats,Brite Adipose Tissues,Brite Fat, Beige,Brite Fats, Beige,Fat, Beige,Fat, Beige Brite,Fat, Brite,Fats, Beige Brite,Tissue, Beige Adipose,Tissue, Brite Adipose,Tissues, Beige Adipose,Tissues, Brite Adipose
D000071256 Uncoupling Protein 1 A mitochondrial uncoupling protein that is expressed in BROWN ADIPOSE TISSUE. It is critical for NONSHIVERING THERMOGENESIS to prevent heat loss in NEONATES. BAT Uncoupling Protein,Brown Adipose Tissue Uncoupling Protein,Mitochondrial Brown Fat Uncoupling Protein 1,Mitochondrial Uncoupling Protein,SLC25A7 Protein,Solute Carrier Family 25 Member 7,Thermogenin,UCP1 Protein,Uncoupling Protein 1a,Uncoupling Protein, Mitochondrial Membrane,Uncoupling Protein, BAT,Uncoupling Protein, Mitochondrial
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001678 Organelle Biogenesis The natural growth and development within living CELLS. Mitochondrial Biogenesis,Biogeneses, Organelle,Biogenesis, Mitochondrial,Biogenesis, Organelle,Organelle Biogeneses
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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