Sexual dimorphism of brown adipose tissue function

ObjectiveTo determine whether brown adipose tissue (BAT) activity in school-age children differs between the sexes and to explore the impact of dietary intake, sedentary behavior, and picky/fussy eating.Study designChildren aged 8.5-11.8 years of age (n = 36) underwent infrared thermography to determine the temperature of the skin overlying the main superficial BAT depot in the supraclavicular region before and after 5 minutes of mild cold exposure (single-hand immersion in cool tap water at about 20°C). The relationships between the supraclavicular region temperature and parental reports of food consumption, eating behavior, and inactivity were explored.ResultsThe supraclavicular region temperature was higher in boys (n = 16) at baseline, and after cold exposure. Boys displayed a greater thermogenic response to cold. Strong negative correlations were observed between the supraclavicular region temperature and body mass index percentile, and differences in supraclavicular region temperature between girls and boys persisted after adjustment for body mass index percentile. A negative linear relationship was observed between protein and vegetable intake and supraclavicular region temperature in girls only, but did not persist after adjustment for multiple comparisons. There was no difference in the adjusted supraclavicular region temperature between active or inactive children, or picky and nonpicky eaters.ConclusionsThese findings indicate sexual dimorphism in BAT thermogenic activity and a sex-specific impact of diet. Future studies should aim to quantify the contribution of BAT to childhood energy expenditure, energy imbalance, and any role in the origins of childhood obesity

Non-phosphorylating Respiration of Mitochondria from Brown Adipose Tissue of Rats

Nonphosphorylating respiration of mitochondria from brown adipose tissue of rat

Brown adipose tissue

Obesity is currently a global pandemic, and is associated with increased mortality and co-morbidities including many metabolic diseases. Obesity is characterized by an increase in adipose mass due to increased energy intake, decreased energy expenditure, or both. While white adipose tissue is specialized for energy storage, brown adipose tissue has a high concentration of mitochondria and uniquely expresses uncoupling protein 1, enabling it to be specialized for energy expenditure and thermogenesis. Although brown fat was once considered only necessary in babies, recent morphological and imaging studies have provided evidence that, contrary to prior belief, this tissue is present and active in adult humans. In recent years, the topic of brown adipose tissue has been reinvigorated with many new studies regarding brown adipose tissue differentiation, function and therapeutic promise. This review summarizes the recent advances, discusses the emerging questions and offers perspective on the potential therapeutic applications targeting this tissue

Recent progress in the study of brown adipose tissue

Brown adipose tissue in mammals plays a critical role in maintaining energy balance by thermogenesis, which means dissipating energy in the form of heat. It is held that in mammals, long-term surplus food intake results in energy storage in the form of triglyceride and may eventually lead to obesity. Stimulating energy-dissipating function of brown adipose tissue in human body may counteract fat accumulation. In order to utilize brown adipose tissue as a therapeutic target, the mechanisms underlying brown adipocyte differentiation and function should be better elucidated. Here we review the molecular mechanisms involved in brown adipose tissue development and thermogenesis, and share our thoughts on current challenges and possible future therapeutic approaches

miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit

Brown adipocytes are a primary site of energy expenditure and reside not only in classical brown adipose tissue but can also be found in white adipose tissue. Here we show that microRNA 155 is enriched in brown adipose tissue and is highly expressed in proliferating brown preadipocytes but declines after induction of differentiation. Interestingly, microRNA 155 and its target, the adipogenic transcription factor CCAAT/enhancer-binding protein beta, form a bistable feedback loop integrating hormonal signals that regulate proliferation or differentiation. Inhibition of microRNA 155 enhances brown adipocyte differentiation and induces a brown adipocyte-like phenotype ('browning') in white adipocytes. Consequently, microRNA 155-deficient mice exhibit increased brown adipose tissue function and 'browning' of white fat tissue. In contrast, transgenic overexpression of microRNA 155 in mice causes a reduction of brown adipose tissue mass and impairment of brown adipose tissue function. These data demonstrate that the bistable loop involving microRNA 155 and CCAAT/enhancer-binding protein b regulates brown lineage commitment, thereby, controlling the development of brown and beige fat cells

Reduced maximum capacity of glycolysis in brown adipose tissue of genetically obese, diabetic (db/db) mice and its restoration following treatment with a thermogenic β-adrenoceptor agonist

AbstractThe maximal activities of the key glycolytic enzymes hexokinase and 6-phosphofructokinase, were reduced in brown adipose tissue in db/db mice compared to their lean littermates. Treatment of db/db mice with the thermogenic β-adrenoceptor agonist, BRL 26830, restored normoglycaemia. The only significant increase in activity of hexokinase and 6-phosphofructokinase in the BRL 26830-treated db/db mice occurred in brown adipose tissue where the total tissue activity increased 10- and 11-fold respectively. These changes together with increased 2-deoxyglucose uptake in vivo suggest that brown adipose tissue can play a quantitatively important role in the removal of glucose from the blood

miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit

Brown adipocytes are a primary site of energy expenditure and reside not only in classical brown adipose tissue but can also be found in white adipose tissue. Here we show that microRNA 155 is enriched in brown adipose tissue and is highly expressed in proliferating brown preadipocytes but declines after induction of differentiation. Interestingly, microRNA 155 and its target, the adipogenic transcription factor CCAAT/enhancer-binding protein b, form a bistable feedback loop integrating hormonal signals that regulate proliferation or differentiation. Inhibition of microRNA 155 enhances brown adipocyte differentiation and induces a brown adipocyte-like phenotype (‘browning’) in white adipocytes. Consequently, microRNA 155- deficient mice exhibit increased brown adipose tissue function and ‘browning’ of white fat tissue. In contrast, transgenic overexpression of microRNA 155 in mice causes a reduction of brown adipose tissue mass and impairment of brown adipose tissue function. These data demonstrate that the bistable loop involving microRNA 155 and CCAAT/enhancer-binding protein b regulates brown lineage commitment, thereby, controlling the development of brown and beige fat cells

Cold exposure induces dynamic, heterogeneous alterations in human brown adipose tissue lipid content

Brown adipose tissue undergoes a dynamic, heterogeneous response to cold exposure that can include the simultaneous synthesis, uptake, and oxidation of fatty acids. The purpose of this work was to quantify these changes in brown adipose tissue lipid content (fat-signal fraction (FSF)) using fat-water magnetic resonance imaging during individualized cooling to 3 °C above a participant’s shiver threshold. Eight healthy men completed familiarization, perception-based cooling, and MRI-cooling visits. FSF maps of the supraclavicular region were acquired in thermoneutrality and during cooling (59.5 ± 6.5 min). Brown adipose tissue regions of interest were defined, and voxels were grouped into FSF decades (0–10%, 10–20%…90–100%) according to their initial value. Brown adipose tissue contained a heterogeneous morphology of lipid content. Voxels with initial FSF values of 60–100% (P \u3c 0.05) exhibited a significant decrease in FSF while a simultaneous increase in FSF occurred in voxels with initial FSF values of 0–30% (P \u3c 0.05). These data suggest that in healthy young men, cold exposure elicits a dynamic and heterogeneous response in brown adipose tissue, with areas initially rich with lipid undergoing net lipid loss and areas of low initial lipid undergoing a net lipid accumulation

Brown Fat in Humans: The Significance of Thermogenic Active Tissue

Brown adipose tissue is a metabolically active form of fat in the body that performs a crucial function in non-shivering thermogenesis. It can be compared to the prevalent white adipose tissue which is generally understood to be energy storage in the body, with brown tissue performing an opposing role. The tissue itself contains unique gene and protein markers such as uncoupling protein 1 (UCP1) which allows for the thermogenic process inside the cell, burning lipids to do so. These gene and protein markers have proven to be crucial in the detection of brown adipose tissue, which had previously been thought to be lost in humans after early childhood. Activation and proliferation of brown adipose tissue has been linked with acute and chronic cold exposure, diet, obesity, age, and more. Ways to increase or monitor this are of considerable interest to the field of obesity studies. Insight into brown adipose tissue corresponds to insights into further energy expenditure processes in the body in areas such as muscles, potentially offering a wide variety of therapeutic options for obesity treatment

Developmental regulation of GLUT-1 (Erytroid/HepG2) and GLUT-4 (Muscle/Fat) glucose transporter expression in rat heart, skeletal muscle, and brown adipose tissue

The expression of GLUT-1 (erythroid/Hep G2) and GLUT-4 (muscle/fat) glucose transporters was assessed during development in rat heart, skeletal muscle, and brown adipose tissue. GLUT-4 protein expression was detectable in fetal heart by day 21 of pregnancy; it increased progressively after birth. attaining levels close to those of adults at day 15 post natal.'In contrast, GLUT-4 messenger RNA (mRNA)was already present in hearts from 17 day-old fetuses. GLUT-4 mRNA stayed low during early postnatal life in heart and brown adipose tissue and only increased after day 10 post natal. The expression pattern for GLUT-4 protein in skeletal muscle during development was comparable to that observed in heart. In contrast to heart and skeletal muscle, GLUT-4 protein in brown adipose tissue was detected in high levels (30% of adult) during late fetal life. During fetal life, GLUT-l presented a very high expression level in brown adipose tissue, heart, and skeletal muscle. Soon after birth, GLUT-1 protein diminished progressively, attaining adult levels at day 10 in heart and skeletal muscle. GLUT-1 mRNA levels in heart followed a similar pattern to the GLUT- 1 protein, being very high during fetal life and decreasing early in post natal life. GLUT-1 protein showed a complex pattern in brown adipose tissue: fetal levels were high, decreased after birth, and increased subsequently in post natal life, reaching a peak by day 9. Progesterone-induced postmaturity protected against the decrease in GLUT-1 protein associated with post natal life in skeletal muscle and brown adipose tissue. However, GLUT-4 induction was not blocked by postmaturity in any of the tissues subjected to study. These results indicate that: 1) during fetal and early post natal life, GLUT-1 is a predominant glucose transporter isotype expressed in heart, skeletal muscle, and brown adipose tissue; 2) during early post natal life there is a generalized GLUT-1 repression; 3) during development, there is a close correlation between protein and mRNA levels for GLUT-l, and therefore regulation at a pretranslational level plays a major regulatory role; 4) the onset of GLUT-4 protein induction occurs between days 20-21 of fetal life; based on data obtained in rat heart and brown adipose tissue, there is a dissociation during development between mRNA and protein levels for GLUT-4, suggesting modifications at translational or posttranslational steps; and 5) postmaturity blocks the decrease in GLUT-l expression but not the induction of GLUT-4. observed soon after birth. All these findings suggest that GLUT-1 repression and GLUT-4 induction are mediated by different mechanisms