scholarly journals Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis

2020 ◽  
Author(s):  
Francisco Javier Ruiz-Ojeda ◽  
Jiefu Wang ◽  
Theresa Bäcker ◽  
Martin Krueger ◽  
Samira Zamani ◽  
...  

AbstractReorganization of the extracellular matrix is a prerequisite for healthy adipose tissue expansion, whereas fibrosis is a key feature of adipose dysfunction and inflammation. However, very little is known about the direct effects of impaired cell-matrix interaction in adipocyte function and insulin sensitivity. Using adipose selective deletion of β1 integrin (Itgb1adipo-cre) and Kindlin-2 (Kind2adipo-cre), we demonstrate here that active β1 and β3 integrins directly interact with the insulin receptor to regulate white adipocyte insulin action and systemic metabolism. Consequently, loss of adipose integrin activity, similar to loss of adipose insulin receptors, results in lipodystrophy and systemic insulin resistance. Conversely, we find that brown adipose tissue of Kind2adipo-cre and Itgb1adipo-cre mice is chronically hyperactivated, and has increased substrate delivery, reduced endothelial basement membrane thickness, and increased endothelial vesicular transport. Thus, we establish integrin-extracellular matrix interactions as key regulators of white and brown adipose tissue function and whole body metabolism.

1993 ◽  
Vol 264 (5) ◽  
pp. R1017-R1023 ◽  
Author(s):  
G. Kortner ◽  
K. Schildhauer ◽  
O. Petrova ◽  
I. Schmidt

To determine developmental changes of brown adipose tissue (BAT) thermogenic activity at defined circadian and thermal states, we evaluated the time course of cold-induced increases of in vitro guanosine 5'-diphosphate (GDP) binding in parallel with whole body metabolism (oxygen consumption, VO2) and core temperature (Tc) in 1- to 11-day-old rat pups. During the maximum phase of the juvenile diurnal cycle, Tc of littermates was recorded continuously and VO2 alternately until 2 min before animals were killed for removal of interscapular BAT. GDP binding after 1.5 h at thermoneutrality and its increase during physiologically comparable cold loads were significantly lower in 1-day-old pups than in 5- and 11-day-old pups. Cold defense was activated more rapidly in the older pups, but GDP binding in even the 1-day-old pups was significantly increased during the second 10-min period of cold exposure. We conclude that rapid changes in thermogenic activity, in connection with the known developmental changes in the dependence of the suckling rat's metabolic cold defense on maternal and sibling contact and circadian phase, will distort longitudinal studies of any fast-changing BAT parameter when the conditions immediately before tissue removal are not thoroughly controlled.


Diabetes ◽  
2014 ◽  
Vol 63 (12) ◽  
pp. 4089-4099 ◽  
Author(s):  
M. Chondronikola ◽  
E. Volpi ◽  
E. Borsheim ◽  
C. Porter ◽  
P. Annamalai ◽  
...  

2016 ◽  
Vol 36 (15) ◽  
pp. 2027-2038 ◽  
Author(s):  
Hongyi Zhou ◽  
Stephen M. Black ◽  
Tyler W. Benson ◽  
Neal L. Weintraub ◽  
Weiqin Chen

Brown adipose tissue (BAT) plays a unique role in regulating whole-body energy homeostasis by dissipating energy through thermogenic uncoupling. Berardinelli-Seip congenital lipodystrophy (BSCL) type 2 (BSCL2; also known as seipin) is a lipodystrophy-associated endoplasmic reticulum membrane protein essential for white adipocyte differentiation. Whether BSCL2 directly participates in brown adipocyte differentiation, development, and function, however, is unknown. We show that BSCL2 expression is increased during brown adipocyte differentiation. Its deletion does not impair the classic brown adipogenic program but rather induces premature activation of differentiating brown adipocytes through cyclic AMP (cAMP)/protein kinase A (PKA)-mediated lipolysis and fatty acid and glucose oxidation, as well as uncoupling. cAMP/PKA signaling is physiologically activated during neonatal BAT development in wild-type mice and greatly potentiated in mice with genetic deletion ofBscl2in brown progenitor cells, leading to reduced BAT mass and lipid content during neonatal brown fat formation. However, prolonged overactivation of cAMP/PKA signaling during BAT development ultimately causes apoptosis of brown adipocytes through inflammation, resulting in BAT atrophy and increased overall adiposity in adult mice. These findings reveal a key cell-autonomous role for BSCL2 in controlling BAT mass/activity and provide novel insights into therapeutic strategies targeting cAMP/PKA signaling to regulate brown adipocyte function, viability, and metabolic homeostasis.


2016 ◽  
Vol 311 (1) ◽  
pp. E95-E104 ◽  
Author(s):  
Aliya Gifford ◽  
Theodore F. Towse ◽  
Ronald C. Walker ◽  
Malcolm J. Avison ◽  
E. Brian Welch

Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [18F]fluorodeoxyglucose ([18F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [18F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means ± SD; 60.2 ± 7.6 vs. 62.4 ± 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; −69.4 ± 11.5 vs. −74.5 ± 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.


2020 ◽  
Author(s):  
Belén Picatoste ◽  
Lucie Yammine ◽  
Rosemary Leahey ◽  
David Soares ◽  
Paul Cohen ◽  
...  

SummaryThe role of brown adipose tissue (BAT) in thermogenesis is widely appreciated, whereas its more recently described role in whole-body metabolism is not as well understood. Here we demonstrate that deletion of Rab10 from brown adipocytes reduces insulin-stimulated glucose transport by inhibiting translocation of the GLUT4 glucose transporter to the plasma membrane. This blunting of glucose uptake into brown adipocytes induces glucose intolerance and insulin-resistance in female but not male mice. The defect in glucose uptake does not affect the thermogenic function of BAT, and the dysregulation of whole-body metabolism is independent of the thermogenic function of BAT, thereby revealing a metabolism-specific role for BAT in female mice. The reduced glucose uptake induced by RAB10 deletion disrupts ChREBP regulation of the expression of de novo lipogenesis-related (DNL) genes, providing a link between DNL in BAT and whole-body metabolic regulation that is independent of thermogenesis.


Author(s):  
Felix T. Yang ◽  
Kristin I. Stanford

Abstract Purpose of Review This review highlights aspects of brown adipose tissue (BAT) communication with other organ systems and how BAT-to-tissue cross-talk could help elucidate future obesity treatments. Recent Findings Until recently, research on BAT has focused mainly on its thermogenic activity. New research has identified an endocrine/paracrine function of BAT and determined that many BAT-derived molecules, termed “batokines,” affect the physiology of a variety of organ systems and cell types. Batokines encompass a variety of signaling molecules including peptides, metabolites, lipids, or microRNAs. Recent studies have noted significant effects of batokines on physiology as it relates whole-body metabolism and cardiac function. This review will discuss batokines and other BAT processes that affect the liver, cardiovascular system, skeletal muscle, immune cells, and brown and white adipose tissue. Summary Brown adipose tissue has a crucial secretory function that plays a key role in systemic physiology.


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