| 1. |
- Betz, Mattias J., et al.
(författare)
-
Presence of Brown Adipocytes in Retroperitoneal Fat From Patients With Benign Adrenal Tumors: Relationship With Outdoor Temperature
- 2013
-
Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:10, s. 4097-4104
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Brown adipose tissue (BAT) is a metabolically highly active organ with increased thermogenic activity in rodents exposed to cold temperature. Recently its presence in the cervical adipose tissue of human adults and its association with a favorable metabolic phenotype have been reported. Objective: The objective of the study was to determine the prevalence of retroperitoneal BAT in human adults. Patients: Fifty-seven patients who underwent surgery for benign adrenal tumors were included in this study. Main Outcome Measures: Prevalence of retroperitoneal BAT adjacent to the removed adrenal tumor as determined by uncoupling protein 1 (UCP1) protein and mRNA expression was measured. Results: Using protein and mRNA expression analysis, we detected UCP1 protein in 26 of 57 patients (45.6%) as well as high mRNA expression of genes characteristic for brown adipocytes, independent of the adrenal tumor type. The presence of brown adipocytes within the retroperitoneal fat was associated with a significantly lower outdoor temperature during the month prior to surgery. Importantly, UCP1 expression on both mRNA and protein level was inversely correlated to outdoor temperature, whereas body mass index, sex, age, and diabetes status were not. Conclusions: These findings suggest that human retroperitoneal adipose tissue can acquire a BAT phenotype, thereby adapting to environmental challenges. These adaptive processes might provide a valuable therapeutic target in the treatment of obesity and insulin resistance.
|
|
| 2. |
- Borga, Magnus, et al.
(författare)
-
Brown adipose tissue in humans: detection and functional analysis using PET (positron emission tomography), MRI (magnetic resonance imaging), and DECT (dual energy computed tomography).
- 2014
-
Ingår i: Methods in enzymology. - : Elsevier. - 1557-7988. ; 537, s. 141-59, s. 141-159
-
Tidskriftsartikel (refereegranskat)abstract
- If the beneficial effects of brown adipose tissue (BAT) on whole body metabolism, as observed in nonhuman experimental models, are to be translated to humans, tools that accurately measure how BAT influences human metabolism will be required. This chapter discusses such techniques, how they can be used, what they can measure and also some of their limitations. The focus is on detection and functional analysis of human BAT and how this can be facilitated by applying advanced imaging technology such as positron emission tomography, magnetic resonance imaging, and dual energy computed tomography.
|
|
| 3. |
- Chondronikola, M., et al.
(författare)
-
Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans
- 2014
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:12, s. 4089-4099
-
Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT(+)) men and five BAT-negative (BAT(-)) men under thermoneutral conditions and after prolonged (5-8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT+ group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans.
|
|
| 4. |
|
|
| 5. |
- Enerbäck, Sven, 1958
(författare)
-
An enzymatic chromatin switch that directs formation of active brown fat
- 2014
-
Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 19:1, s. 3-4
-
Tidskriftsartikel (refereegranskat)abstract
- How is the recruitment of brown adipocytes regulated? Ohno et al. (2013) show that the euchromatic histone-lysine N-metyltransferase 1 (EHMT1) is essential for the specification of the brown adipocyte fate, a finding with important implications for the pathophysiology of obesity and obesity-related maladies. © 2014 Elsevier Inc.
|
|
| 6. |
- Enerbäck, Sven, 1958
(författare)
-
Brown adipose tissue in humans
- 2010
-
Ingår i: INTERNATIONAL JOURNAL OF OBESITY. - 0307-0565. ; 34
-
Forskningsöversikt (refereegranskat)abstract
- Obesity is endemic in many regions of the world and a forerunner of several serious and sometimes fatal diseases such as ischemic heart disease, stroke, kidney failure and neoplasia. Although we know its origin—it results when energy intake exceeds energy expenditure—at present, the only proven therapy is bariatric surgery. This is a major abdominal procedure that, for reasons that are largely unknown (it cannot be explained solely by a reduction in ventricular volume), significantly reduces energy intake, but because of cost and limited availability, it will most likely be reserved for only a small fraction of those who stand to gain from effective antiobesity treatment. Clearly, alternative ways to treat obesity are needed. Another way to combat excessive accumulation of white adipose tissue would be to increase energy expenditure. Rodents, hibernators and human infants all have a specialized tissue—brown adipose tissue (BAT)—with the unique capacity to regulate energy expenditure by a process called adaptive thermogenesis. This process depends on the expression of uncoupling protein-1 (UCP1), which is a unique marker for BAT. UCP1 is an inner mitochondrial membrane protein that short circuits the mitochondrial proton gradient, so that oxygen consumption is no longer coupled to adenosine triphosphate synthesis. As a consequence, heat is generated. Mice lacking ucp-1 are severely compromised in their ability to maintain normal body temperature when acutely exposed to cold and they are also prone to become obese. We have shown that, in mice, BAT protects against diet-induced obesity, insulin resistance and type 2 diabetes. This is based on prevention of excessive accumulation of triglyceride in non-adipose tissues such as muscle and liver. Ectopic triglyceride storage at these locations is associated with initiation of insulin resistance and, ultimately, development of type 2 diabetes.
|
|
| 7. |
- Enerbäck, Sven, 1958
(författare)
-
Human brown adipose tissue.
- 2010
-
Ingår i: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 11:4, s. 248-52
-
Tidskriftsartikel (refereegranskat)abstract
- The BAT organ is unique in that it has evolved to safely dissipate large amounts of chemical energy--a quality that might be harnessed to help humans deal with a dangerously hypercaloric environment and still remain in good health.
|
|
| 8. |
- Gnad, T., et al.
(författare)
-
Adenosine activates brown adipose tissue and recruits beige adipocytes via A(2A) receptors
- 2014
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 516:7531
-
Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies(1-5). Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of beta-adrenergic receptors(1-5). Because BAT therapies based on cold exposureor beta-adrenergic agonists are clinically not feasible, alternative strategies must be explored. Purinergic co-transmission might be involved in sympathetic control of BAT and previous studies reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat(6-8). However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A(2A) receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A(2A) receptors in mice causes adecrease in BAT-dependent thermogenesis, whereas treatment with A(2A) agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A(2A) receptors or injection of lentiviral vectors expressing the A(2A) receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A(2A) agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine-A(2A) signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies.
|
|
| 9. |
- Håkansson, Joakim, 1975, et al.
(författare)
-
Adipocyte mitochondrial genes and the forkhead factor FOXC2 are decreased in type 2 diabetes patients and normalized in response to rosiglitazone.
- 2011
-
Ingår i: Diabetology & metabolic syndrome. - : Springer Science and Business Media LLC. - 1758-5996. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: FOXC2 has lately been implicated in diabetes and obesity as well as mitochondrial function and biogenesis and also as a regulator of mtTFA/Tfam. In this study, the expression of FOXC2 and selected genes involved in mitochondrial function and biogenesis in healthy subjects and in a matched cohort with type 2 diabetes patients before and after treatment with rosiglitazone was determined. Quantitative real time PCR was used to analyze both RNA and DNA from biopsies from subcutaneous adipose tissue. METHODS: Blood samples and subcutaneous abdominal fat biopsies were collected from 12 T2D patients, of which 11 concluded the study, pre-treatment and 90 days after initiation of rosiglitazone treatment, and from 19 healthy control subjects on the first and only visit from healthy subjects. Clinical parameters were measured on the blood samples. RNA and DNA were prepared from the fat biopsies and gene expression was measured with real time PCR. RESULTS: The expression level of genes in the mitochondrial respiratory complexes I - IV were significantly downregulated in the diabetic patients and restored in response to rosiglitazone treatment. Rosiglitazone treatment also increased the relative number of mitochondria in diabetic patients compared with controls. Furthermore, the transcription factors FOXC2 and mtTFA/Tfam displayed a response pattern identical to the mitochondrial genes. CONCLUSIONS: FOXC2, mtTFA/Tfam and subunits of the respiratory complexes I - IV show equivalent regulation in gene expression levels in response to TZD treatment. This, together with the knowledge that FOXC2 has a regulatory function of mtTFA/Tfam and mitochondrial biogenesis, suggests that FOXC2 has a possible functional role in the TZD activated mitochondrial response.
|
|
| 10. |
- Karlsson, Mona, et al.
(författare)
-
Pilot Study of Sentinel-Node-Based Adoptive Immunotherapy in Advanced Colorectal Cancer.
- 2010
-
Ingår i: Annals of surgical oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 17:7, s. 1747-1757
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite optimal surgical treatment and modern adjuvant therapies, 50% of patients diagnosed with colorectal cancer die within 5 years. Immunotherapy offers an appealing complement to traditional chemotherapy, with possible long-term protection against tumor recurrences through immunological memory. We have conducted a pilot study of a novel adoptive immunotherapy, using autologous, in vitro expanded lymphocytes isolated from the tumor-draining sentinel lymph node. STUDY DESIGN: Sentinel nodes were recovered from 16 patients with disseminated or locally advanced, high-risk colorectal cancer. Single-cell suspensions of sentinel-node-acquired lymphocytes were clonally expanded in vitro in the presence of autologous tumor extract and returned as a transfusion. Patients were followed with clinical and radiological evaluations. Long-term survival was compared with traditionally treated controls. RESULTS: Sentinel-node-acquired CD4(+) Th1-lymphocytes could be clonally expanded in vitro and safely administered to all 16 patients without side-effects. In four out of nine stage IV patients, complete tumor regression occurred. Median survival time in the stage IV patients (n = 9) was 2.6 years, as compared with 0.8 years in conventionally treated controls. A dose-dependent effect with regards to reduced tumor burden and long-term survival was observed. CONCLUSION: Sentinel-node-based adoptive immunotherapy is feasible; the method has shown no apparent side-effects and appears to convey therapeutic antitumor effects. Further studies are justified to determine its efficacy and precise role in the treatment of colorectal cancer.
|
|
