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

Abstract

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.

A Critical Review on the Role of Food and Nutrition in the Energy Balance

“…Green (unroasted) coffee and roasted coffee contain the same amount of caffeine (1.2%-2.2%) but a different percentage of chlorogenic acids (6.5%-10% vs 2.7%-3.1%, respectively) [54]. Caffeine increases thermogenesis and energy expenditure by several mechanisms [55,56]. In humans, the thermic effect lasts about 150 min after a single-dose caffeine ingestion [56] and one RCT reported a stronger metabolic impact among habitual low consumers of caffeine, thus suggesting the possibility of a long-term insensitivity to the effects of caffeine after high and prolonged exposure [57].…”

“…In cultured adipocytes, caffeine has been shown to enhance BAT function and thermogenesis by up-regulating UCP1 and BAT-selective regulatory genes including PPAR-γ, PPAR-γ coactivator (PGC)-1α and PR domain containing 16 (PRDM16) [55]. PGC-1α also induces mitochondrial biogenesis and stimulates fatty-acid oxidation and oxygen consumption through the co-activation of PPAR-γ [55].…”

“…In cultured adipocytes, caffeine has been shown to enhance BAT function and thermogenesis by up-regulating UCP1 and BAT-selective regulatory genes including PPAR-γ, PPAR-γ coactivator (PGC)-1α and PR domain containing 16 (PRDM16) [55]. PGC-1α also induces mitochondrial biogenesis and stimulates fatty-acid oxidation and oxygen consumption through the co-activation of PPAR-γ [55]. Caffeine induces PGC1α and UCP1 indirectly as well, by antagonizing the transient receptor potential vanilloid (TRPV)-4, a negative regulator of PGC-1α in the TRPV receptor family and a modulator of beige/brown adipocyte thermogenesis [55].…”

“…PGC-1α also induces mitochondrial biogenesis and stimulates fatty-acid oxidation and oxygen consumption through the co-activation of PPAR-γ [55]. Caffeine induces PGC1α and UCP1 indirectly as well, by antagonizing the transient receptor potential vanilloid (TRPV)-4, a negative regulator of PGC-1α in the TRPV receptor family and a modulator of beige/brown adipocyte thermogenesis [55]. Adipose tissue browning is additionally stimulated through the expression of other specific genes (CD137, LHX8, P2RX5, CITED1 and COX8b) [55].…”

The Role of Coffee Consumption in the Treatment of Obesity

“…Bu konuda, en güncel veri 2019 yılında yapılmış bir çalışmaya ait olup; buna göre kafeinin kahverengi yağ dokusu fonksiyonunu uyardığı rapor edilmiştir. 43 Kahve, adipozitlerin farklılaşmasına etki etmesinin yanı sıra, lipid metabolizmasında görevli nükleer reseptörlerle ilişkili olan peroksizom proliferatör aktifleştirici reseptör γ ekspresyonu üzerine etki etmektedir. 44 Ayrıca, kahve ve kafein ise iştah üzerindeki baskılayıcı etkileriyle obezite ile ilişkilendirilmektedir.…”