Amount Of Brown Adipose Tissue Research Articles

Lipopolysaccharide-binding protein is a negative regulator of adipose tissue browning in mice and humans.

Adipocyte lipopolysaccharide-binding protein (LBP) biosynthesis is associated with obesity-induced adipose tissue dysfunction. Our purpose was to study the role of LBP in regulating the browning of adipose tissue. Adult mice were maintained at 4°C for 3 weeks or treated with the β3-adrenergic agonist, CL316,243, for 1 week to induce the browning of white fat. Precursor cells from brown and white adipose tissues were cultured under differentiation-inducing conditions to yield brown and beige/brite adipocytes, respectively. In vitro, Lbp was knocked down in 3T3-L1 adipocytes, and cells were treated with recombinant LBP or co-cultured in transwells with control 3T3-L1 adipocytes. Wild-type and Lbp-null mice, fed a standard or high fat diet (HFD) for 15weeks, were also used in investigations. In humans, subcutaneous and visceral adipose tissue samples were obtained from a cohort of morbidly obese participants. The induction of white fat browning by exposure of mice to cold or CL316,243 treatment was strongly associated with decreased Lbp mRNA expression in white adipose tissue. The acquisition of the beige/brite phenotype in cultured cells was associated with downregulation of Lbp. Moreover, silencing of Lbp induced the expression of brown fat-related genes in adipocytes, whereas LBP treatment reversed this effect. Lbp-null mice exhibited the spontaneous induction of subcutaneous adipose tissue browning, as evidenced by a remarkable increase in Ucp1 and Dio2 gene expression and the appearance of multivacuolar adipocyte clusters. The amount of brown adipose tissue, and brown adipose tissue activity were also increased in Lbp-null mice. These changes were associated with decreased weight gain in Lbp-null mice and protection against HFD-induced inflammatory responses, as shown by reduced IL-6 levels. However, rather than improving glucose homeostasis, these effects led to glucose intolerance and insulin resistance. LBP is identified as a negative regulator of the browning process, which is likely to contribute to the obesity-promoting action of LBP. The deleterious metabolic effects of LBP deletion are compatible with the concept that the appropriate regulation of inflammatory pathways is necessary for a healthy systemic metabolic profile, regardless of body weight regulation.

Investigation of Gender Effect on Obesity using a Model of Inbreed Obese Mouse Lines by Fourier Transform Infrared Imaging

Lipid accumulation and storage of lipids in adipocytes during obesity cause structural and functional changes in adipose tissue conformation. The expansion of visceral (VAT) and subcutaneous (SCAT) adipose tissue mass in the body is the main reason of obesity and many times it results in disturbed lipid and glucose metabolism. Gender is an important factor for the research in obesity and other metabolic diseases because it leads to different fat distribution and the pathophysiology. This study aims to determine gender effect on the structural and functional parameters on VAT and SCAT. To achieve this, FTIR microspectroscopic imaging technique and UCP1 immunohistological staining have been used. FTIR microspectroscopy is a rapid and effective technique to monitor molecular alterations in biological tissues induced by different conditions such as disease, chemical treatment and variations in the environmental factors. UCP1 protein content gives information about the amount of brown adipose tissue (BAT), and therefore about the transdifferentiation of BAT to the white adipose tissue (WAT). The results of FTIR imaging study revealed a decrease in unsaturation level of lipids and an increase in the amount of triglycerides in adipose tissue samples. Furhermore, the longer hydrocarbon acyl chain length was obtained in the lipids of obese samples. All of these spectral paramaters could be used as biomarkers in obesity. The results of the present study showed that, these obesity indicators are more significant in SAT of female mice, whilst, they are more significant inVAT of male mice. The amount of UCP1 protein which is a marker of the transdifferentiation, showed a decrease in male samples rather than females. Consequently, obesity has adverse effects on health of both genders but especially on men.

Protein tyrosine phosphatase profiling studies during brown adipogenic differentiation of mouse primary brown preadipocytes

There is a correlation between obesity and the amount of brown adipose tissue; however, the molecular mechanism of brown adipogenic differentiation has not been as extensively studied. In this study, we performed a protein tyrosine phosphatase (PTP) profiling analysis during the brown adipogenic differentiation of mouse primary brown preadipocytes. Several PTPs, including PTPRF, PTPRZ, and DUSP12 showing differential expression patterns were identified. In the case of DUSP12, the expression level is dramatically downregulated during brown adipogenesis. The ectopic expression of DUSP12 using a retroviral expression system induces the suppression of adipogenic differentiation, whereas a catalytic inactive DUSP12 mutant showed no effect on differentiation. These results suggest that DUSP12 is involved in brown adipogenic differentiation and may be used as a target protein for the treatment or prevention of obesity by the regulation of brown adipogenic differentiation. [BMB Reports 2013; 46(11): 539-543]

Dual-Specificity Phosphatase 10 Controls Brown Adipocyte Differentiation by Modulating the Phosphorylation of P38 Mitogen-Activated Protein Kinase

BackgroundBrown adipocytes play an important role in regulating the balance of energy, and as such, there is a strong correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism underlying white adipocyte differentiation has been well characterized, brown adipocyte differentiation has not been studied extensively. Here, we investigate the potential role of dual-specificity phosphatase 10 (DUSP10) in brown adipocyte differentiation using primary brown preadipocytes.Methods and ResultsThe expression of DUSP10 increased continuously after the brown adipocyte differentiation of mouse primary brown preadipocytes, whereas the phosphorylation of p38 was significantly upregulated at an early stage of differentiation followed by steep downregulation. The overexpression of DUSP10 induced a decrease in the level of p38 phosphorylation, resulting in lower lipid accumulation than that in cells overexpressing the inactive mutant DUSP10. The expression levels of several brown adipocyte markers such as PGC-1α, UCP1, and PRDM16 were also significantly reduced upon the ectopic expression of DUSP10. Furthermore, decreased mitochondrial DNA content was detected in cells expressing DUSP10. The results obtained upon treatment with the p38 inhibitor, SB203580, clearly indicated that the phosphorylation of p38 at an early stage is important in brown adipocyte differentiation. The effect of the p38 inhibitor was partially recovered by DUSP10 knockdown using RNAi.ConclusionsThese results suggest that p38 phosphorylation is controlled by DUSP10 expression. Furthermore, p38 phosphorylation at an early stage is critical in brown adipocyte differentiation. Thus, the regulation of DUSP10 activity affects the efficiency of brown adipogenesis. Consequently, DUSP10 can be used as a novel target protein for the regulation of obesity.

A maternal diet of fatty fish reduces body fat of offspring compared with a maternal diet of beef and a post‐weaning diet of fish improves insulin sensitivity and lipid profile in adult C57BL/6 male mice

The maternal diet during pregnancy and lactation may affect the long-term health of the offspring. Our aim was to study how a fish or meat diet perinatal and after weaning affects body composition, insulin sensitivity and the profile of n-3 and n-6 polyunsaturated fatty acids (PUFAs) in breast milk, fat depots, skeletal muscle and liver in male adult mice offspring. During gestation and lactation, C57BL/6 dams were fed a herring- or beef-based diet. Half of the pups in each group changed diets after weaning. In offspring, body composition measured by DEXA, plasma lipid profile and insulin sensitivity measured by euglycemic clamp or QUICKI were monitored to adulthood. Analysis of total FAs by GC-MS were performed in the diet, breast milk and in different tissues. At 9week of age, offspring of herring-fed dams had less body fat than offspring of beef-fed dams. Mice fed herring after weaning had increased insulin sensitivity at 15week of age, reduced total plasma cholesterol and triglyceride levels, and compared with beef-fed mice, larger interscapular brown adipose tissue depots. The FA composition of the maternal diet was mirrored in breast milk, and the herring diet significantly affected the FA profile of different tissues, leading to an increased content of n-3 PUFAs. A herring-based maternal diet reduces body fat in the offspring, but the insulin sensitivity, plasma lipids and amount of brown adipose tissue are affected by the offspring's own diet; the herring diet is more beneficial than the beef diet.

4E‐BP1 regulates the differentiation of white adipose tissue

4E Binding protein 1 (4E-BP1) suppresses translation initiation. The absence of 4E-BP1 drastically reduces the amount of adipose tissue in mice. To address the role of 4E-BP1 in adipocyte differentiation, we characterized 4E-BP1(-/-) mice in this study. The lack of 4E-BP1 decreased the amount of white adipose tissue and increased the amount of brown adipose tissue. In 4E-BP1(-/-) MEF cells, PPARγ coactivator 1 alpha (PGC-1α) expression increased and exogenous 4E-BP1 expression suppressed PGC-1α expression. The level of 4E-BP1 expression was higher in white adipocytes than in brown adipocytes and showed significantly greater up-regulation in white adipocytes than in brown adipocytes during preadipocyte differentiation into mature adipocytes. The amount of PGC-1α was consistently higher in HB cells (a brown preadipocyte cell line) than in HW cells (a white preadipocyte cell line) during differentiation. Moreover, the ectopic over-expression of 4E-BP1 suppressed PGC-1α expression in white adipocytes, but not in brown adipocytes. Thus, the results of our study indicate that 4E-BP1 may suppress brown adipocyte differentiation and PGC-1α expression in white adipose tissues.

Prevalence, Mass, and Glucose-Uptake Activity of 18F-FDG-Detected Brown Adipose Tissue in Humans Living in a Temperate Zone of Italy

BackgroundThe 18F-fluorodeoxyglucose (18F-FDG)-detected brown adipose tissue (BAT), is enhanced by cold stimulus and modulated by other factors that still have to be disentangled. We investigated the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in a population of adults living in the temperate climatic zone of the Rome area.Methods and FindingsWe retrospectively analyzed 6454 patients who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) examinations. We found 18F-FDG BAT in 217 of the 6454 patients (3.36%). Some of them underwent more than one scan and the positive scans were 278 among 8004 (3.47%). The prevalence of patients with at least one positive scan was lower in men (1.77%; 56 of 3161) compared with women (4.88%; 161 of 3293). The BAT positive patients were most frequently younger, thinner and with lower plasma glucose levels compared with BAT negative patients. The amount of BAT in the defined region of interest, the activity of BAT and the number of positive sites of active BAT were similar in both sexes. The prevalence of patients with 18F-FDG positive PET/CT was highest in December-February, lower in March-May and September-November, and lowest in June-August and was positively correlated with night length and negatively correlated with ambient temperature. Changes in day length and variations of temperature, associated with the prevalence of positive BAT patients. Among the patients who had multiple scans, outdoor temperature was significantly lower and day length was shorter on the occasion when BAT was detected.ConclusionsThis study identifies day length, outdoor temperature, age, sex, BMI, and plasma glucose levels as major determinants of the prevalence, mass, and activity of 18F-FDG-detected BAT.

Core Concepts: Thermoregulation in the Newborn Part I: Basic Mechanisms

Support and regulation of the thermal environment of the newborn have long been recognized as critical aspects of newborn care, and they have become increasingly important as smaller and less mature infants are able to survive. In this review, the foundational work done more than 50 years ago that defined the impact of hypothermia on morbidity and mortality in infants is discussed, and the concept of the neutral thermal environment is described, as well as how the identification of a narrow range of body temperature in which metabolic and oxygen demands are at their lowest has ensured safety in infant care while facilitating growth and optimal outcome. Thermoregulation is discussed within the framework of a balance between heat production and loss. The unique physiologic mechanisms that are available to the newborn to reduce loss and produce extra heat when facing a cold stress are described. The relatively large amount of brown adipose tissue in the newborn is a key energy source for heat production, although the metabolic processes and control mechanisms surrounding nonshivering thermogenesis differ between the more vulnerable premature infant and the term infant. In contrast to the means of heat production, the capacity of the newborn for self-protection against heat loss is limited. Without external support, newborns can readily lose heat and body temperature through all four mechanisms of heat loss, including evaporation, conduction, radiation, and convection, although each plays a greater or lesser role at various times after birth. Unless measures are taken to minimize these losses, severe physiologic derangements may result.

Arcuate NPY Controls Sympathetic Output and BAT Function via a Relay of Tyrosine Hydroxylase Neurons in the PVN

Neuropepetide Y (NPY) is best known for its powerful stimulation of food intake and its effects on reducing energy expenditure. However, the pathways involved and the regulatory mechanisms behind this are not well understood. Here we demonstrate that NPY derived from the arcuate nucleus (Arc) is critical forthe control of sympathetic outflow and brown adipose tissue (BAT) function. Mechanistically,a key change induced by Arc NPY signaling is a marked Y1 receptor-mediated reduction in tyrosine hydroxylase (TH) expression in the hypothalamic paraventricular nucleus (PVN), which is also associated with a reduction in TH expression in the locus coeruleus (LC) and other regions in the brainstem. Consistent with this, Arc NPY signaling decreased sympathetically innervated BAT thermogenesis, involving the downregulation of uncoupling protein 1 (UCP1) expression in BAT. Taken together, these data reveal a powerful Arc-NPY-regulated neuronal circuit that controls BAT thermogenesis and sympathetic output via TH neurons.

The adipose organ at a glance

The main parenchymal cells of the adipose organ are adipocytes. White adipocytes store energy, whereas brown adipocytes dissipate energy for thermogenesis. These two cell types with opposing functions can both originate from endothelial cells, and co-exist in the multiple fat depots of the adipose organ – a feature that I propose is crucial for this organ’s plasticity. This poster review provides an overview of the adipose organ, describing its anatomy, cytology, physiological function and histopathology in obesity. It also highlights the remarkable plasticity of the adipose organ, explaining theories of adipocyte transdifferentiation during chronic cold exposure, physical exercise or lactation, as well as in obesity. White-to-brown adipocyte transdifferentiation is of particular medical relevance, because animal data indicate that higher amounts of brown adipose tissue are positively associated with resistance to obesity and its co-morbidities, and that ‘browning’ of the adipose organ curbs these disorders.

Anatomical and Functional Assessment of Brown Adipose Tissue by Magnetic Resonance Imaging

Brown adipose tissue (BAT) is the primary tissue responsible for nonshivering thermogenesis in mammals. The amount of BAT and its level of activation help regulate the utilization of excessive calories for thermogenesis as opposed to storage in white adipose tissue (WAT) which would lead to weight gain. Over the past several years, BAT activity in vivo has been primarily assessed by positron emission tomography-computed tomography (PET-CT) scan using 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) to measure glucose utilization associated with BAT mitochondrial respiration. In this study, we demonstrate the feasibility of mapping and estimating BAT volume and metabolic function in vivo in rats at a 9.4T magnetic resonance imaging (MRI) scanner using sequences available from clinical MR scanners. Based on the morphological characteristics of BAT, we measured the volume distribution of BAT with MRI sequences that have strong fat-water contrast. We also investigated BAT volume by utilizing spin-echo MRI sequences. The in vivo MRI-estimated BAT volumes were correlated with direct measurement of BAT mass from dissected samples. Using MRI, we also were able to map hemodynamic responses to changes in BAT metabolism induced pharmacologically by β3-adrenergic receptor agonist, CL-316,243 and compare this to BAT activity in response to CL-316,243 assessed by PET 18F-FDG. In conclusion, we demonstrate the feasibility of measuring BAT volume and function in vivo using routine MRI sequences. The MRI measurement of BAT volume is consistent with quantitative measurement of the tissue ex vivo.

The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes

White and brown adipocytes are believed to occupy different sites in the body. We studied the anatomical features and quantitative histology of the fat depots in obesity and type 2 diabetes-prone C57BL/6J mice acclimated to warm or cold temperatures. Most of the fat tissue was contained in depots with discrete anatomical features, and most depots contained both white and brown adipocytes. Quantitative analysis showed that cold acclimation induced an increase in brown adipocytes and an almost equal reduction in white adipocytes; however, there were no significant differences in total adipocyte count or any signs of apoptosis or mitosis, in line with the hypothesis of the direct transformation of white into brown adipocytes. The brown adipocyte increase was accompanied by enhanced density of noradrenergic parenchymal nerve fibers, with a significant correlation between the density of these fibers and the number of brown adipocytes. Comparison with data from obesity-resistant Sv129 mice disclosed a significantly different brown adipocyte content in C57BL/6J mice, suggesting that this feature could underpin the propensity of the latter strain to develop obesity. However, the greater C57BL/6J browning capacity can hopefully be harnessed to curb obesity and type 2 diabetes in patients with constitutively low amounts of brown adipose tissue.

PAZ6 Cells Constitute a Representative Model for Human Brown Pre-Adipocytes

The role of brown adipose tissue (BAT) in human metabolism and its potential as an anti-obesity target organ have recently received much renewed attention. Following radiological detection of substantial amounts of BAT in adults by several independent research groups, an increasing number of studies are now dedicated to uncover BAT’s genetic, developmental, and environmental determinants. In contrast to murine BAT, human BAT is not present as a single major fat depot in a well-defined location. The distribution of BAT in several areas in the body significantly limits its availability to research. A human brown adipocyte cell line is therefore critical in broadening the options available to researchers in the field. The human BAT-cell line PAZ6 was created to address such a need and has been well characterized by several research groups around the world. In the present review, we discuss their findings and propose potential applications of the PAZ6 cells in addressing the relevant questions in the BAT field, namely for future use in therapeutic applications.

Myostatin inhibits brown adipocyte differentiation via regulation of Smad3-mediated β-catenin stabilization

Brown adipocytes play an important role in regulating energy balance, and there is a good correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism of white adipocyte differentiation has been well characterized, brown adipogenesis has not been studied extensively. Moreover, extracellular factors that regulate brown adipogenic differentiation are not fully understood. Here, we assessed the mechanism of the regulatory action of myostatin in brown adipogenic differentiation using primary brown preadipocytes. Our results clearly showed that differentiation of brown adipocytes was significantly inhibited by myostatin treatment. In addition, myostatin-induced suppression of brown adipogenesis was observed during the early phase of differentiation. Myostatin induced the phosphorylation of Smad3, which led to increased β-catenin stabilization. These effects were blocked by treatment with a Smad3 inhibitor. Expression of brown adipocyte-related genes, such as PPAR-γ, UCP-1, PGC-1α, and PRDM16, were dramatically down-regulated by treatment with myostatin, and further down-regulated by co-treatment with a β-catenin activator. Taken together, the present study demonstrated that myostatin is a potent negative regulator of brown adipogenic differentiation by modulation of Smad3-induced β-catenin stabilization. Our findings suggest that myostatin could be used as an extracellular factor in the control of brown adipocyte differentiation.

Association between the presence of brown adipose tissue and non‐alcoholic fatty liver disease in adult humans

The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.

Three years with adult human brown adipose tissue

The presence of active brown adipose tissue in adult humans has been recognized in general physiology only since 2007. The intervening three years established that the depots originally observed by (18)F-fluoro-deoxy-glucose positron emission tomography (FDG PET) scanning techniques really are brown adipose tissue depots because they are enriched for uncoupling protein 1 (UCP1). Reports of low apparent prevalence of brown adipose tissue based on retrospective studies of hospital records of FDG PET scans markedly underestimate true prevalence because such studies only reflect acute activity state; consequently, such retrospective studies cannot be conclusively analysed for factors influencing activity and amount of brown adipose tissue. Dedicated studies show that the true prevalence is 30-100%, depending on cohort. Warm temperature during the investigation-as well as adrenergic antagonists-inhibit tissue activity. There is probably no sexual dimorphism in the prevalence of brown adipose tissue. Outdoor temperature may affect the amount of brown adipose tissue, and the amount is negatively correlated with age and obesity. The presence of brown adipose tissue is associated with cold-induced nonshivering thermogenesis, and the tissue may be a major organ for glucose disposal. The decline in brown adipose tissue amount with increasing age may account for or aggravate middle-age obesity. Maintained activation of brown adipose tissue throughout life may thus protect against obesity and diabetes.

Mitochondrial DNA: An Up‐and‐coming Actor in White Adipose Tissue Pathophysiology

Mitochondrial DNA: An Up‐and‐coming Actor in White Adipose Tissue Pathophysiology

Identification and Importance of Brown Adipose Tissue in Adult Humans

Although brown adipose tissue in infants and young children is important for regulation of energy expenditure, there has been considerable debate on whether brown adipose tissue normally exists in adult humans and has physiologic relevance in this population. In the last decade, radiologic studies in adults have identified areas of adipose tissue with high 18F-fluorodeoxyglucose (18F-FDG) uptake, putatively identified as brown fat. This radiologic study assessed the presence of physiologically significant brown adipose tissue among 1972 adult patients who had 3640 consecutive 18F-FDG positron-emission tomographic and computed tomographic whole-body scans between 2003 and 2006. Brown adipose tissue was defined as areas of tissue that were more than 4 mm in diameter, had the CT density of adipose tissue, and had maximal standardized uptake values of 18F-FDG of at least 2.0 gm per mL. A sample of 204 date-matched patients without brown adipose tissue served as the control group. Using these criteria, positron-emission tomographic and computed tomographic scans identified brown adipose tissue in 106 of the 1972 patients (5.4%). The most common location for substantial amounts of brown adipose tissue was the region extending from the anterior neck to supraclavicular region. Immunohistochemical staining for uncoupling protein 1 in this region confirmed the identity of immunopositive, multilocular adipocytes as brown adipose tissue. More brown adipose tissue was detected in women (7.5% {lsqb;76/1013{rsqb;) than in men (3.1% {lsqb;30/959{rsqb;); the female:male ratio was 2.4:1.0 (P < 0.001). The mass and activity of brown adipose tissue was also greater in women than in men. The probability of having substantial brown adipose tissue decreased with increasing age (<50–>64) (P < 0.001), short-term or long-term use of beta-blockers (P < 0.001), increasing mean outdoor temperature at the time of the scan (P < 0.02), and increasing tissue and increasing body mass index among patients in the top third for age (>64 years) (P for trend = 0.007). These findings show that functional brown adipose tissue is prevalent in adult humans, and significantly more frequently in women. The inverse correlation of body mass index with the amount of brown adipose tissue, especially in older patients, suggests to the investigators a possible role of brown adipose tissue in protecting against obesity.

Identification and Importance of Brown Adipose Tissue in Adult Humans

Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007). Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.

Hormone-Sensitive Lipase Knockouts

All treatments for obesity, including dietary restriction of carbohydrates, have a goal of reducing the storage of fat in adipocytes. The chief enzyme responsible for the mobilization of FFA from adipose tissue, i.e., lipolysis, is thought to be hormone-sensitive lipase (HSL). Studies of HSL knockouts have provided important insights into the functional significance of HSL and into adipose metabolism in general. Studies have provided evidence that HSL, though possessing triacylglycerol lipase activity, appears to be the rate-limiting enzyme for cholesteryl ester and diacylglycerol hydrolysis in adipose tissue and is essential for complete hormone stimulated lipolysis, but other triacylglycerol lipases are important in mediating triacylglycerol hydrolysis in lipolysis. HSL knockouts are resistant to both high fat diet-induced and genetic obesity, displaying reduced quantities of white with increased amounts of brown adipose tissue, increased numbers of adipose macrophages, and have multiple alterations in the expression of genes involved in adipose differentiation, including transcription factors, markers of adipocyte differentiation, and enzymes of fatty acid and triglyceride synthesis. With disruption of lipolysis by removal of HSL, there is a drastic reduction in lipogenesis and alteration in adipose metabolism.