Whitening and Impaired Glucose Utilization of Brown Adipose Tissue in a Rat Model of Type 2 Diabetes Mellitus

Lapa, Constantin; Arias-Loza, Paula; Hayakawa, Nobuyuki; Wakabayashi, Hiroshi; Werner, Rudolf A.; Chen, Xinyu; Shinaji, Tetsuya; Herrmann, Ken; Pelzer, Theo; Higuchi, Takahiro

doi:10.1038/s41598-017-17148-w

Cited by 48 publications

(43 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, it has been suggested that diet‐induced obesity might cause functional hypoxia in BAT ultimately leading to a functional shift from thermogenesis toward lipid storage . Our data exploring BAT content and gene expression resonate with previous studies showing that exposure to hypercaloric diets enlarges the interscapular BAT depot and does not alter Ucp‐1 or Cidea expression but reduces the expression of Pgc‐1α , suggesting an impaired mitochondrial function upon caloric overload. As previously stated, there is consensus about the potential of Foxc2 in counteracting diet‐induced insulin resistance .…”

Section: Discussionsupporting

confidence: 89%

“…In basal conditions, brown adipocytes have the ability to release energy as heat in a process mediated by UCP-1 (21). Recently, it has been suggested that diet-induced obesity might cause functional hypoxia in BAT ultimately leading to a functional shift from thermogenesis toward lipid storage (22,23). Our data exploring BAT content and gene expression resonate with previous studies showing that exposure to hypercaloric diets enlarges the interscapular BAT depot (22,23) and does not alter Ucp-1 or Cidea expression (23,24) but reduces the expression of Pgc-1α (24), suggesting an impaired mitochondrial function upon caloric overload.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of Free‐Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety‐Like Behavior in Rats

Peris-Sampedro

Mounib

Schéle

et al. 2019

Obesity

View full text Add to dashboard Cite

Objective Rats were exposed to free‐choice diets (fat plus one of two different sugar solutions, glucose or sucrose), and the metabolic consequences and impact on locomotor activity and anxiety‐like behavior were explored. Methods For 3 weeks, 7‐week‐old male rats were offered either chow only or free‐choice high‐fat diets differing in their added sugar: no sugar, sucrose, or glucose. In a second experiment, after 2 weeks on the diets, rats were switched from high sucrose to high glucose for two additional weeks. Metabolic end points included body weight, food intake, food choice, glycemic control, metabolic hormones, fat pad weight, brown adipose tissue weight, and gene expression. Behavioral analysis included locomotor and anxiety‐like activity in the open field and elevated plus maze. Results Both sugar diets enhanced adiposity and induced hyperphagia, favoring unhealthier dietary selection above that of the control diets (chow or free‐choice high‐fat with no sugar). Despite isocaloric intake in the sugar‐containing diets, offering glucose instead of sucrose was associated with improved insulin sensitivity. The sugar‐containing diets reduced activity (but with movements of increased velocity) and induced an anxiety‐like phenotype. Conclusions Although free‐choice diets negatively impacted on metabolism and anxiety‐like behavior, replacing sucrose with glucose improved insulin sensitivity and may therefore be better for health.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Impact of Free‐Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety‐Like Behavior in Rats

Peris-Sampedro

Mounib

Schéle

et al. 2019

Obesity

View full text Add to dashboard Cite

show abstract

“…Because obesity has been associated with structural and functional “whitening” of brown adipose depots in rodents (11–14), we performed experiments to confirm that the tissue expansion in SM/J mice has the expected properties of brown fat. Histological analysis of the fat depot taken from high fat-fed SM/J mice at 30 weeks of age confirms the adipocytes in this expansion are brown adipocytes, with small multilocular lipid droplets and high UCP1 staining ( Supplemental Figure 3C-J ).…”

Section: Resultsmentioning

confidence: 99%

Brown adipose expansion and remission of glycemic dysfunction in obese SM/J mice

Carson

Macias-Velasco

Gunawardana

et al. 2019

Preprint

View full text Add to dashboard Cite

52Disruption of glucose homeostasis increases the risk of type II diabetes, cardiovascular disease, stroke, 53 and cancer. We leverage a novel rodent model, the SM/J mouse, to understand glycemic control in 54 obesity. On a high fat diet, obese SM/J mice initially develop impaired glucose tolerance and elevated 55 fasting glucose. Strikingly, their glycemic dysfunction resolves by 30 weeks of age despite persistence of 56 obesity. A prominent phenotype is that they dramatically expand their brown adipose depots as they 57 resolve glycemic dysfunction. This occurs naturally and spontaneously on a high fat diet, with no 58 temperature or genetic manipulation. When the brown adipose depot is removed from normoglycemic 59 obese mice, fasting blood glucose and glucose tolerance revert to unhealthy levels, and animals become 60 insulin resistant. We identified 267 genes whose expression changes in the brown adipose when the 61 mice resolve their unhealthy glycemic parameters, and find the expanded tissue has a 'healthier' 62 expression profile of cytokines and extracellular matrix genes. We describe morphological, physiological, 63 and transcriptomic changes that occur during the unique brown adipose expansion and remission of 64 glycemic dysfunction in obese SM/J mice. Understanding this phenomenon in mice will open the door for 65 innovative therapies aimed at improving glycemic control in obesity.66 67 Significance Statement 68 Some obese individuals maintain normal glycemic control. Despite being obese, these individuals 69 have low risk for metabolic complications, including type-II diabetes. If we better understood why some 70 obese people maintain normoglycemia then we might develop new approaches for treating metabolic 71 complications associated with obesity. However, the causative factors underlying glycemic control in 72 obesity remain unknown. We discovered that, despite persistence of the obese state, SM/J mice enter 73 into diabetic remission: returning to normoglycemia and reestablishing glucose tolerance and improving 74 insulin sensitivity. A prominent phenotype is that they dramatically expand their brown adipose depots as 75 they resolve glycemic dysfunction. Understanding this phenomenon in mice will open the door for 76 innovative therapies aimed at improving glycemic control in obesity. 78An estimated 10-30% of obese individuals maintain glycemic control and some longitudinal 79 studies suggest their risk of developing type II diabetes is no greater than matched lean individuals (1). 80No causative factors underlying glycemic control in obesity have been discovered, however the strongest 81 predictors of impaired glycemic control in obesity are increased visceral fat mass and adipose tissue 82 dysfunction (2,3). Thus research efforts have focused on understanding the genetic and physiological 83 mechanisms of action of adipose. Recent research reveals that brown adipose activity is associated with 84 anti-diabetic properties. Cold exposure in both obese and lean individuals causes increased uptake...

show abstract

“…Most of the secreted proteins were detected in cell culture media from both brown and white adipocytes ( Figure 1G), but interestingly, vascular endothelial growth factor A (VEGFA) was only identified in the media from brown adipocytes while leptin (LEP) was exclusively identified in white adipocytes (Table S1). This provides proof of concept of our experimental workflow as LEP is one of the most studied white fat-derived hormones (Stern et al, 2016) while VEGFA is a wellestablished brown fat growth factor (Park et al, 2017;Shimizu et al, 2017).…”

Section: The Secretome Of Human Brown and White Adipocytesmentioning

confidence: 68%

Proteomics-based comparative mapping of the human brown and white adipocyte secretome reveals EPDR1 as a novel batokine

Deshmukh

Peijs

Nielsen

et al. 2018

Preprint

View full text Add to dashboard Cite

Secreted proteins from adipose tissue play a role in metabolic cross-talk and homeostasis. We performed high sensitivity mass spectrometry-based proteomics on the cell media of in vitro differentiated, non-immortalized brown adipocytes derived from supraclavicular adipose of adult humans and white adipocytes derived from subcutaneous adipose of adult humans. We identified 471 potentially secreted proteins covering interesting protein categories such as hormones, growth factors, growth factor binding proteins, cytokines, extracellular matrix proteins, and proteins of the complement system, which were differentially regulated in brown and white adipocytes. A total of 101 proteins were exclusively quantified in brown adipocytes, among these ependymin-related protein 1 (EPDR1). Ablation of EPDR1 impaired the induction of thermogenic transcripts in response to norepinephrine in brown adipocytes, while EPDR1-treated mice increased their energy consumption, suggesting a role in brown fat commitment and activation. Our work reveals substantial differences between the secretomes of brown and white human adipocytes and identifies novel candidate batokines.the degradation of the alternative C3 convertase (C3bBb). In addition, CFH acts as a cofactor to 20045).Ollikainen, M., 2017. Subcutaneous adipose tissue gene expression and DNA methylation respond to both short-and long-term weight loss. Int. J. Obes. 1-12.

show abstract

Whitening and Impaired Glucose Utilization of Brown Adipose Tissue in a Rat Model of Type 2 Diabetes Mellitus

Cited by 48 publications

References 32 publications

Impact of Free‐Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety‐Like Behavior in Rats

Impact of Free‐Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety‐Like Behavior in Rats

Brown adipose expansion and remission of glycemic dysfunction in obese SM/J mice

Proteomics-based comparative mapping of the human brown and white adipocyte secretome reveals EPDR1 as a novel batokine

Contact Info

Product

Resources

About