adipose tissue (BAT) from white adipose tissue (WAT) in rats using spectral computed tomography (CT) with histological validation.MATERIALS AND METHODS: A lipid-containing phantom (lipid fractions from 0% to 100%) was imaged with spectral CT. An in vivo, non-enhanced spectral CT scan was performed on 24 rats, and fat concentrations of BAT and WAT were measured. The rats were randomized to receive intraperitoneal treatment with norepinephrine (NE) (n = 12) or saline (n = 12). Non-enhanced and enhanced spectral CT scans were performed after treatment to measure the elevation of iodine in BAT and WAT. The BAT/aorta and WAT/aorta ratios were calculated and compared, after which isolated BAT and WAT samples were subjected to histological and uncoupling protein 1 (UCP1) analyses.RESULTS: The ex-vivo phantom study showed excellent linear fit between measured fat concentration and the known gravimetric reference standard (r² = 0.996). In vivo, BAT had significantly lower fat concentration than WAT (p < 0.001). Compared to the saline group, the iodine concentration of BAT increased significantly (p < 0.001) after injection of NE, while the iodine concentration of WAT only changed slightly. The BAT/aorta ratio also increased significantly after exposure to NE compared to the saline group (p < 0.001). Histological and UCP1 expression analyses supported the spectral CT imaging results.CONCLUSION: The study consolidates spectral CT as a new approach for non-invasive imaging of BAT and WAT. Quantitative analyses of BAT and WAT by spectral CT revealed different characteristics and pharmacologic activations in the two types of adipose tissue.]]>
Adipose Tissue ; Adipose Tissue, Brown ; Adipose Tissue, White ; Animals ; Iodine ; Norepinephrine ; Rats ; Tomography, X-Ray Computed

Brown adipose tissue (BAT) is regarded as a key target for developing interventions to prevent and treat obesity and age-related diseases. In addition, uncoupling pro tein 1 (UCP1)
Adipocytes ; Adipose Tissue ; Adipose Tissue, Brown ; Adipose Tissue, White ; Atrophy ; Eating ; Humans ; Middle Aged ; Obesity ; Thermogenesis

Lipoblastoma is a rare benign mesenchymal tumor that exhibits a tendency to invade locally but not to metastasize, and develops from embryonic remnants of white fat tissue. We experienced a case of lipoblastoma occurring in a 7-month-old girl. A small nodule developed on her right inguinal region at the age of 4 months. It had grown to be a 1.2x2.0cm in size, well-defined, volcano-like, ovoid erythematous nodule. Histopathologically it was composed of well-defined lobulated fat tissue with multivacuolated lipoblasts, undifferentiated mesenchymal cells such as stellate or spindle cells and minimal myxoid stroma. Electron microscopic findings demonstrated lipoblasts with eccentric nuclei and coarse chromatins. Complete local excision was done.
Adipose Tissue, White ; Chromatin ; Female ; Humans ; Infant ; Lipoblastoma*

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.
Adipocytes, Beige ; cytology ; Adipose Tissue, Brown ; cytology ; metabolism ; Adipose Tissue, White ; cytology ; Aging ; metabolism ; Animals ; Humans

Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability and vascularization. Additional factors that influence adipose tissue heterogeneity are genetic predisposition, environment, gender and age. Under obese condition, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. For instance, individuals with central obesity are more susceptible to developing diabetes and cardiovascular complications, whereas those with peripheral obesity are more metabolically healthy. This review summarizes the clinical and mechanistic evidence for the depot-specific differences that give rise to different metabolic consequences, and provides therapeutic insights for targeted treatment of obesity.
Adipose Tissue ; Adipose Tissue, White* ; Genetic Predisposition to Disease ; Glucose ; Insulin Resistance ; Lipid Metabolism ; Obesity ; Obesity, Abdominal ; Population Characteristics*

Brown adipose generates heat via oxidation of fatty acids by a mitochondrial uncoupling protein 1 (UCP1)-dependent process. In addition, a subpopulation of cells within subcutaneous white adipose tissue, known as beige adipocytes, also plays a role in thermogenesis. The biogenesis of beige adipocytes is induced by thermogenic signals, such as chronic cold exposure. Recently, it has been reported that eosinophils, type 2 cytokines of IL-4/13, and alternatively activated macrophages control the thermogenic cycle of beige adipocytes. Alternatively, activated macrophages induce UCP1+ beige adipocytes through secretion of catecholamines. These results define the role of type 2 immune responses in the regulation of energy homeostasis.
Adipocytes ; Adipose Tissue, Brown ; Adipose Tissue, White ; Organelle Biogenesis* ; Catecholamines ; Cytokines ; Eosinophils* ; Fatty Acids ; Homeostasis ; Hot Temperature ; Macrophages* ; Thermogenesis

OBJECTIVE: To investigate the time-sequential expression of a novel long non-coding RNA, lnc AK079912, in metabolically related tissues and during adipose tissue development and browning in mice. METHODS: The interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue (sWAT), epididymal white adipose tissue (eWAT), liver tissues and muscular tissues were collected from 8-week-old C57BL/6J mice. The iBAT, sWAT and eWAT were also collected from the mice during development (0 day, 21 days, 8 weeks and 6 months after birth) and from 8- to 10-week- mice with cold exposure (4 ℃) and intraperitoneal injections of CL316, 243 (1 μg/g body weight) for 1 to 5 days. Trizol was used to extract the total RNA from the tissues, and RT-qPCR was performed to detect the expressions of lnc AK079912. Isolated mouse preadipocytes in primary culture were induced for adipogenic differentiation for 9 days and then treated with CL316, 243 (2 μmol/L) for different durations (no longer than 24 h); the expression of lnc AK079912 in the cells was detected using RT-qPCR at different time points of the treatment. RESULTS: Lnc AK079912 was highly expressed in mouse adipose tissues, the highest in iBAT, followed by the muscular tissue, but was hardly detected in the liver tissue. The expression level of lnc AK079912 increased progressively in iBAT and sWAT during development of the mice, while its expression in eWAT showed an initial increase followed by a reduction at 8 weeks ( < 0.001). No significant difference was found in the expression of lnc AK079912 in the iBAT, sWAT or eWAT in mice with cold stimulation for 1 to 5 days ( > 0.05). The expression of lnc AK079912 was significantly decreased in iBAT and eWAT ( < 0.05) but increased in eWAT from mice with intraperitoneal injection of CL316, 243 for 1 to 5 days ( < 0.05). The expression level in the adipocytes in primary culture was significantly increased in response to treatment with CL316, 243 ( < 0.05). CONCLUSIONS Lnc AK079912 is highly expressed in mouse adipose tissue, and its expression gradually increases with the development of adipose tissue but with a depot-specific difference. Lnc AK079912 is significantly elevated in the early stage of adipose tissue browning, indicating its important role in the development and browning of adipose tissue.
Adipocytes ; Adipogenesis ; Adipose Tissue, Brown ; Adipose Tissue, White ; Animals ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Long Noncoding

To characterize the timeliness of β3 adrenergic receptor agonist CL316,243-induced browning of white adipose tissues in mice.
 Methods: Male C57BL/6J mice at 10 weeks of age were housed in conventional cages and given sterile saline for the control group or CL316,243 (1 μg/g) for the experimental group via intraperitoneal injection for 1, 3, and 5 days. Food intake and body weight were measured daily. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous white adipose (sWAT) and epididymal white adipose tissue (eWAT) were harvested for histological and gene expression analysis.
 Results: Compared with the control group, intraperitoneal injection of CL316,243 reduced the weight of eWAT on the first day. Meanwhile, CL316,243 continuously promoted the mRNA and protein expression of uncoupling protein-1 (UCP-1) in sWAT and eWAT. Furthermore, CL316,243 injection significantly decreased the food intake and weight gain of the mice, and reduced the diameter of adipocyte and accumulation of small lipid droplets in adipose tissues.
 Conclusion: CL316,243 can induce the brown-like remodeling in adipose tissues of mice in vivo, which show different time-dependent manners in different adipose tissues.
Adipose Tissue, Brown ; Adipose Tissue, White ; Adrenergic beta-Agonists ; Animals ; Male ; Mice ; Mice, Inbred C57BL ; Uncoupling Protein 1

This study investigated the mechanism of Zexie Decoction(ZXD) in promoting white adipose tissue browning/brown adipose tissue activation based on the GLP-1R/cAMP/PKA/CREB pathway. A hyperlipidemia model was induced by a western diet(WD) in mice, and the mice were divided into a control group, a model group(WD), and low-, medium-, and high-dose ZXD groups. An adipogenesis model was induced in 3T3-L1 cells in vitro, and with forskolin(FSK) used as a positive control, low-, medium-, and high-dose ZXD groups were set up. Immunohistochemistry and immunofluorescence results showed that compared with the WD group, ZXD promoted the expression of UCP1 in white and brown adipose tissues, and also upregulated UCP1, CPT1β, PPARα, and other genes in the cells. Western blot analysis showed a dose-dependent increase in the protein expression of PGC-1α, UCP1, and PPARα with ZXD treatment, indicating that ZXD could promote the white adipose tissue browning/brown adipose tissue activation. Hematoxylin-eosin(HE) staining results showed that after ZXD treatment, white and brown adipocytes were significantly reduced in size, and the mRNA expression of ATGL, HSL, MGL, and PLIN1 was significantly upregulated as compared with the results in the WD group. Oil red O staining and biochemical assays indicated that ZXD improved lipid accumulation and promoted lipolysis. Immunohistochemistry and immunofluorescence staining for p-CREB revealed that ZXD reversed the decreased expression of p-CREB caused by WD. In vitro intervention with ZXD increased the protein expression of CREB, p-CREB, and p-PKA substrate, and increased the mRNA level of CREB. ELISA detected an increase in intracellular cAMP concentration with ZXD treatment. Molecular docking analysis showed that multiple active components in Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma could form stable hydrogen bond interactions with GLP-1R. In conclusion, ZXD promotes white adipose tissue browning/brown adipose tissue activation both in vivo and in vitro, and its mechanism of action may be related to the GLP-1R/cAMP/PKA/CREB pathway.
Mice ; Animals ; Adipose Tissue, Brown ; Molecular Docking Simulation ; PPAR alpha/metabolism* ; Adipose Tissue, White ; RNA, Messenger/metabolism*

Adipose tissue is a central metabolic organ that controls energy homeostasis of the whole body. White adipose tissue (WAT) stores excess energy in the form of triglycerides, whereas brown adipose tissue (BAT) dissipates energy in the form of heat through mitochondrial uncoupling protein 1 (Ucp1). A newly identified adipose tissue called ‘beige fat’ (BAT-like) is produced through a process called WAT browning. This tissue mainly resides in WAT depots and displays intermediate characteristics of both WAT and BAT. Since the recent discovery of BAT in the human body, along with the identification of molecular targets for BAT activation, stimulating energy expenditure has been considered as a great strategy to treat human obesity and metabolic diseases. Here we summarize recent findings regarding molecular targets and thermogenic small molecules that can stimulate BAT and increase energy expenditure, with an emphasis on possible therapeutic applications in humans.
Adipocytes* ; Adipose Tissue ; Adipose Tissue, Brown ; Adipose Tissue, White ; Energy Metabolism ; Homeostasis ; Hot Temperature ; Human Body ; Humans ; Metabolic Diseases ; Obesity ; Triglycerides