scholarly journals Brown Adipose Tissue Remodeling Precedes Cardiometabolic Abnormalities Independent of Overweight in Fructose-Feed Mice

2019 ◽  
Author(s):  
Thaissa Queiroz Machado ◽  
Debora Cristina Pereira-Silva ◽  
Leidyanne Ferreira Gonçalves ◽  
Caroline Fernandes-Santos

AbstractObjectivesTo investigate the early cardiometabolic abnormalities along with WAT and BAT remodeling in short-term fructose feeding mice model.MethodsMice (n=10-11/group) were fed for four weeks with control diet (AIN93-M) or experimental diets rich in glucose or fructose. We investigated body weight, body adiposity, blood glucose, lipid and hepatic parameters, and white (WAT) and brown adipose tissue (BAT) histopathology.ResultsFructose feeding promoted neither weight gain nor hypertrophy of visceral and subcutaneous WAT depots, but the fat was redistributed toward visceral depots. Glucose, lipid and hepatic metabolic dysfunction were not yet noticed in fructose-fed mice, with the exception for an elevation in total cholesterol and hepatic weight without steatosis. BAT mass did not increase, and it was proportionally reduced compared with visceral WAT in fructose feed mice. BAT suffered premature adverse morphological remodeling, characterized by increased lipid deposition per tissue area in enlarged intracellular lipid droplets.ConclusionShort-term fructose feeding redistributes body fat, changes the proportion of BAT to visceral fat, and promotes BAT adverse remodeling, characterized by enlarged intracellular lipid droplets.

Author(s):  
Machado TQ ◽  
Pereira-Silva DC ◽  
Goncalves LF ◽  
Fernandes-Santos C

Background: Body fat distribution is a risk factor for several health conditions, although the literature shows that excess body fat is not always associated with cardiometabolic abnormalities in all subjects.Objectives: To investigate glucose, lipid, and hepatic metabolism, along with white (WAT) and brown adipose tissue (BAT) remodeling in a mice model of short-term fructose feeding.Methods: Male C57BL/6 mice (n = 10-11/group) were fed for four weeks with control diet (AIN93-M) or experimental diets rich in glucose or fructose. We investigated body weight, body adiposity, blood glucose, lipid and hepatic parameters, and WAT and BAT histopathology.Results: Fructose feeding did not promote either weight gain or adipocyte hypertrophy of visceral and subcutaneous WAT depots, but the fat was redistributed toward visceral depots. Fructose-fed mice did not show glucose, lipid, and hepatic metabolic dysfunction, except for an elevation in total cholesterol and hepatic weight. BAT mass did not increase, and it was proportionally reduced compared with visceral WAT in fructose feed mice. BAT suffered early adverse morphological remodeling, characterized by increased lipid deposition and enlargement of intracellular lipid droplets.Conclusion: Short-term fructose feeding redistributes fat among WAT depots, alters the ratio between BAT andvisceral WAT, and promotes BAT adverse remodeling, characterized by enlarged intracellular lipid droplets.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ryutaro Ikegami ◽  
Ippei Shimizu ◽  
Takeshi Sato ◽  
Shuang Jiao ◽  
Yohko Yoshida ◽  
...  

Accumulating evidence suggests that adult humans possess active brown adipose tissue (BAT) that may contribute significantly to systemic metabolism because of its high energy consumption capacity. Recently, we demonstrated that metabolic stress induced BAT hypoxia and impaired mitochondrial function, leading to the development of BAT “whitening” and systemic metabolic dysfunction in murine obese models. Various neurotransmitters are known to be involved in the maintenance of BAT homeostasis. Among them, the gamma-aminobutyric acid (GABA) signaling in the central nervous system is well accepted to have anti-obesity effects through the activation of the sympathetic nervous system. Here we show the previously unknown role of peripheral GABA signaling in the development of systemic metabolic dysfunction in obesity. We generated an obese model by imposing a high fat/high sucrose (HFHS) diet on C57BL/6NCr mice. Mass spectrometry analysis demonstrated a significant increase in GABA level in BAT of the dietary obese model. Addition of GABA into drinking water induced BAT whitening, reduced the thermogenic response upon cold tolerance test, and promoted systemic metabolic dysfunction in the obese mice. Mitochondrial calcium is important for the maintenance of mitochondrial homeostasis, whereas calcium overload is reported to inhibit mitochondrial function. Treatment of BAT cells with GABA markedly increased mitochondrial calcium level, promoted the production of reactive oxygen species (ROS), and inhibited mitochondrial respiration. These results indicate that peripheral GABA contributes to the development of systemic metabolic dysfunction by inhibiting BAT function in obesity. The inhibition of peripheral GABA signaling would become a new therapeutic target for obesity and diabetes.


1992 ◽  
Vol 70 (1) ◽  
pp. 171-179 ◽  
Author(s):  
John S. Hayward ◽  
Paul A. Lisson

Species from all extant families of marsupials and monotremes were examined to clarify whether these mammalian subclasses possess brown adipose tissue. To optimize the chance of finding this tissue, special emphasis was given to sampling species adapted to colder regions, species with small adult body size, and individuals at a stage of development equivalent to the newborn stage of placentals (late pouch life in the case of marsupials). Evidence based on gross morphology and light, electron, and fluorescence microscopy failed to show the presence of brown adipose tissue in any marsupial or monotreme. All adipose tissue was typical white fat, including special instances where multilocularity of lipid droplets occurred in association with white adipocyte development or with fat mobilization resulting from nutritional or cold stress. These results, combined with lack of positive identification of brown adipose tissue in birds or other vertebrates, indicate that brown adipose tissue is unique to eutherian (placental) mammals and probably evolved early in the radiation of this subclass. This uniqueness presents the opportunity to suggest a more satisfactory name for the subclass: Thermolipia (from the Greek for "warm fat") or, commonly, thermolipials.


Author(s):  
Peter Aldiss ◽  
Jo Lewis ◽  
David Boocock ◽  
Amanda Miles ◽  
Ian Bloor ◽  
...  

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n = 12) were fed either a standard (10% fat, n = 6) or high fat diet (HFD: 45% fat, n = 6) for 72 h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72 h induced rapid weight gain (c. 2.6%) and reduced serum NEFA with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and PPAR signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g. Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.


2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Nicholas Wawrzyniak ◽  
Andrew Duarte ◽  
Linda Nguyen ◽  
Anna‐Maria Joseph ◽  
Andrew Layne ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1065 ◽  
Author(s):  
Peter Aldiss ◽  
Jo E. Lewis ◽  
David J. Boocock ◽  
Amanda K. Miles ◽  
Ian Bloor ◽  
...  

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n=12) were fed either a standard (10% fat, n=6) or high fat diet (HFD: 45% fat, n=6) for 72h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72h induced rapid weight gain (c. 2.6%) and reduced serum non-esterified fatty acids (NEFA) with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and peroxisome proliferator-activated receptor (PPAR) signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g., Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.


1985 ◽  
Vol 248 (1) ◽  
pp. E20-E25 ◽  
Author(s):  
M. Saito ◽  
Y. Minokoshi ◽  
T. Shimazu

The interscapular brown adipose tissue (IBAT) from obese rats with lesions of the ventromedial hypothalamus (VMH) was approximately 5 times heavier than those from controls. This hypertrophy of IBAT was associated with a marked enlargement of constituent adipocytes and their apparent transformation from multiloculated structure of lipid droplets into the uniloculated structure. The rate of fatty acid synthesis in IBAT of the obese rats was less than one-tenth of that in control rats and approximated the value in white adipose tissue (WAT) when they were starved for 24 h. When rats were fed, the synthetic rate was increased, but the lipogenic response of IBAT in the obese rats was much greater than that in controls, the extent of the response being comparable to that of WAT. The IBAT temperature rose rapidly on electrical stimulation of the sympathetic nerves to the tissue in control rats, whereas the temperature response was reduced markedly in the obese rats. It was suggested that thermogenesis in BAT was impaired in obese rats with VMH lesions by decreasing triglyceride turnover in BAT, probably due to dysfunction of the sympathetic nervous system and a consequent transformation of BAT into WAT.


2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Wenjing You ◽  
Ziye Xu ◽  
Ye Sun ◽  
Teresa G. Valencak ◽  
Yizhen Wang ◽  
...  

Abstract Stress can lead to obesity and metabolic dysfunction, but the underlying mechanisms are unclear. Here we identify GADD45α, a stress-inducible histone folding protein, as a potential regulator for brown adipose tissue biogenesis. Unbiased transcriptomics data indicate a positive correlation between adipose Gadd45a mRNA level and obesity. At the cellular level, Gadd45a knockdown promoted proliferation and lipolysis of brown adipocytes, while Gadd45a overexpression had the opposite effects. Consistently, using a knockout (Gadd45a−/−) mouse line, we found that GADD45α deficiency inhibited lipid accumulation and promoted expression of thermogenic genes in brown adipocytes, leading to improvements in insulin sensitivity, glucose uptake, energy expenditure. At the molecular level, GADD45α deficiency increased proliferation through upregulating expression of cell cycle related genes. GADD45α promoted brown adipogenesis via interacting with PPARγ and upregulating its transcriptional activity. Our new data suggest that GADD45α may be targeted to promote non-shivering thermogenesis and metabolism while counteracting obesity.


Sign in / Sign up

Export Citation Format

Share Document