scholarly journals Metabolic dysfunction induced by high-fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice

2021 ◽  
Author(s):  
Kyle T Mincham ◽  
Kunjal Panchal ◽  
Prue H Hart ◽  
Robyn M Lucas ◽  
Martin Feelisch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Progenitor Cells ◽  
Immune Cells ◽  
High Fat Diet ◽  
Low Dose ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Hematopoietic Stem ◽  
Brown Adipose

AbstractBrown adipose tissue (BAT) may be an important metabolic regulator of whole-body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little known is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPC) – which give rise to DCs – in bone marrow, with less known of its effects in BAT. We have previously demonstrated that ongoing exposure to low-dose ultraviolet radiation (UVR) significantly reduced the ‘whitening’ effect of eating a high-fat diet upon interscapular (i)BAT of mice. Here, we examined whether this observation may be linked to changes in the phenotype of HSPC and myeloid-derived immune cells in iBAT and bone marrow of mice using 12-colour flow cytometry. Many HSPC subsets declined in both iBAT and bone marrow with increasing metabolic dysfunction. Conversely, with rising adiposity and metabolic dysfunction, conventional (c)DCs increased in both of these tissues. When compared to low-fat diet, consumption of high-fat diet significantly reduced proportions of myeloid, common myeloid and megakaryocyte-erythrocyte progenitors in iBAT, and short-term hematopoietic stem cells in bone marrow. In mice fed a high-fat diet, exposure to low-dose UVR significantly reduced proportions of cDCs in iBAT, independently of nitric oxide release from irradiated skin (blocked using the scavenger, cPTIO), but did not significantly modify HSPC subsets in either tissue. Further studies are needed to determine whether changes in these cell populations contribute towards metabolic dysfunction.

scholarly journals Adipocyte Utx Deficiency Promotes High-Fat Diet-Induced Metabolic Dysfunction in Mice

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 181
Author(s):  
Fenfen Li ◽  
Shirong Wang ◽  
Xin Cui ◽  
Jia Jing ◽  
Liqing Yu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Chow Diet ◽  
Main Function ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Brown Adipose

While the main function of white adipose tissue (WAT) is to store surplus of energy as triacylglycerol, that of brown adipose tissue (BAT) is to burn energy as heat. Epigenetic mechanisms participate prominently in both WAT and BAT energy metabolism. We previously reported that the histone demethylase ubiquitously transcribed tetratricopeptide (Utx) is a positive regulator of brown adipocyte thermogenesis. Here, we aimed to investigate whether Utx also regulates WAT metabolism in vivo. We generated a mouse model with Utx deficiency in adipocytes (AUTXKO). AUTXKO animals fed a chow diet had higher body weight, more fat mass and impaired glucose tolerance. AUTXKO mice also exhibited cold intolerance with an impaired brown fat thermogenic program. When challenged with high-fat diet (HFD), AUTXKO mice displayed adipose dysfunction featured by suppressed lipogenic pathways, exacerbated inflammation and fibrosis with less fat storage in adipose tissues and more lipid storage in the liver; as a result, AUTXKO mice showed a disturbance in whole body glucose homeostasis and hepatic steatosis. Our data demonstrate that Utx deficiency in adipocytes limits adipose tissue expansion under HFD challenge and induces metabolic dysfunction via adipose tissue remodeling. We conclude that adipocyte Utx is a key regulator of systemic metabolic homeostasis.

scholarly journals Low-dose UV radiation before running wheel access activates brown adipose tissue

2020 ◽  
Vol 244 (3) ◽  
pp. 473-486 ◽  
Author(s):  
Tristan S Allemann ◽  
Gursimran K Dhamrait ◽  
Naomi J Fleury ◽  
Tamara N Abel ◽  
Prue H Hart ◽  
...  
Keyword(s):  
Physical Activity ◽  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
High Fat Diet ◽  
Low Dose ◽  
High Fat ◽  
Running Wheel ◽  
Brown Adipose ◽  
Running Wheels

In previous preclinical studies, low (non-burning) doses of UV radiation (UVR) limited weight gain and metabolic dysfunction in mice fed with a high-fat diet. Here, we explored the effects of low-dose UVR on physical activity and food intake and mechanistic pathways in interscapular brown adipose tissue (iBAT). Young adult C57Bl/6J male mice, housed as individuals, were fed a high-fat diet and exposed to low-dose UVR (sub-oedemal, 1 kJ/m2 UVB, twice-a-week) or ‘mock’ treatment, with or without running wheel access (2 h, for ‘moderate’ physical activity) immediately after phototherapy. There was no difference in distance run in mice exposed to UVR or mock-treated over 12 weeks of exposure to running wheels (P = 0.14). UVR (alone) did not significantly affect food intake, adiposity, or signs of glucose dysfunction. Access to running wheels increased food intake (after 10 weeks, P ≤ 0.02) and reduced gonadal white adipose tissue and iBAT mass (P ≤ 0.03). Body weight and hepatic steatosis were lowest in mice exposed to UVR with running wheel access. In the iBAT of mice exposed to UVR and running wheels, elevated Atgl, Cd36, Fasn, Igf1, Pparγ, and Ucp1 mRNAs and reduced CD11c on F4-80 + MHC class II+ macrophages were observed, while renal Sglt2 mRNA levels were increased, compared to high-fat diet alone (P ≤ 0.03). Blood levels of 25-hydroxyvitamin D were not increased by exposure to UVR and/or access to running wheels. In conclusion, when combined with physical activity, low-dose UVR may more effectively limit adiposity (specifically, body weight and hepatic steatosis) and modulate metabolic and immune pathways in iBAT.

Brown adipose tissue metabolism in ob/ob mice: effects of a high-fat diet and adrenalectomy

1987 ◽  
Vol 253 (2) ◽  
pp. E149-E157
Author(s):  
H. K. Kim ◽  
D. R. Romsos
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
High Fat ◽  
Adipose Tissue Metabolism ◽  
High Carbohydrate ◽  
Bat Mitochondria ◽  
Norepinephrine Turnover ◽  
Brown Adipose ◽  
Thermogenic Capacity

Adrenalectomy prevents development of obesity in ob/ob mice fed high-carbohydrate stock diets partly by stimulating the low thermogenic capacity of their brown adipose tissue (BAT). Adrenalectomy, however, fails to prevent development of obesity in ob/ob mice fed a high-fat diet. Effects of adrenalectomy on BAT metabolism in ob/ob mice fed a high-fat diet were thus examined. ob/ob mice fed the high-fat diet developed gross obesity despite normal BAT metabolism, as assessed by rates of norepinephrine turnover in BAT, GDP binding to BAT mitochondria, and GDP-inhibitable, chloride-induced mitochondrial swelling. Adrenalectomy failed to arrest the development of obesity or to influence BAT metabolism in ob/ob mice fed the high-fat diet. Development of obesity in ob/ob mice fed a high-fat diet is not associated with low thermogenic capacity of BAT or with adrenal secretions, as it is in ob/ob mice fed high-carbohydrate stock diets.

scholarly journals Female adipose tissue-specific Bscl2 knockout mice develop only moderate metabolic dysfunction when housed at thermoneutrality and fed a high-fat diet

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
George D. Mcilroy ◽  
Sharon E. Mitchell ◽  
Weiping Han ◽  
Mirela Delibegović ◽  
Justin J. Rochford
Keyword(s):  
Adipose Tissue ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Tissue Specific

scholarly journals Protective Effects of Individual and Combined Low Dose Beta-Carotene and Metformin Treatments against High-Fat Diet-Induced Responses in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3607
Author(s):  
Bojan Stojnić ◽  
Alba Serrano ◽  
Lana Sušak ◽  
Andreu Palou ◽  
M. Luisa Bonet ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Beta Carotene ◽  
Protective Effects ◽  
High Fat ◽  
Cumulative Energy ◽  
Brown Adipose ◽  
Obesogenic Diet ◽  
Cumulative Energy Intake

Anti-obesity activity has been reported for beta-carotene (BC) supplementation at high doses and metformin (MET). We studied whether BC treatment at a closer to dietary dose and MET treatment at a lower than therapeutic dose are effective in ameliorating unwanted effects of an obesogenic diet and whether their combination is advantageous. Obesity-prone mice were challenged with a high-fat diet (HFD, 45% energy as fat) for 4 weeks while receiving a placebo or being treated orally with BC (3 mg/kg/day), MET (100 mg/kg/day), or their combination (BC+MET); a fifth group received a placebo and was kept on a normal-fat diet (10% energy as fat). HFD-induced increases in body weight gain and inguinal white adipose tissue (WAT) adipocyte size were attenuated maximally or selectively in the BC+MET group, in which a redistribution towards smaller adipocytes was noted. Cumulative energy intake was unaffected, yet results suggested increased systemic energy expenditure and brown adipose tissue activation in the treated groups. Unwanted effects of HFD on glucose control and insulin sensitivity were attenuated in the treated groups, especially BC and BC+MET, in which hepatic lipid content was also decreased. Transcriptional analyses suggested effects on skeletal muscle and WAT metabolism could contribute to better responses to the HFD, especially in the MET and BC+MET groups. The results support the benefits of the BC+MET cotreatment.

PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Yu-Wen Cheng ◽  
Ze-Bei Zhang ◽  
Bei-Di Lan ◽  
Jing-Rong Lin ◽  
Xiao-Hui Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Cardiac Remodeling ◽  
High Fat Diet ◽  
Platelet Derived Growth Factor ◽  
Obese Mice ◽  
Mechanistic Studies ◽  
High Fat ◽  
Cardiac Damage ◽  
First Time

Obesity-induced secretory disorder of adipose tissue–derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)–infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow–specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.

α1-Antitrypsin A treatment attenuates neutrophil elastase accumulation and enhances insulin sensitivity in adipose tissue of mice fed a high-fat diet.

2021 ◽  
Author(s):  
Randall F. D'Souza ◽  
Stewart W.C. Masson ◽  
Jonathan S. T. Woodhead ◽  
Samuel L James ◽  
Caitlin MacRae ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Neutrophil Elastase ◽  
High Fat Diet ◽  
Tolerance Test ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Insulin Tolerance

Neutrophils accumulate in insulin sensitive tissues during obesity and may play a role in impairing insulin sensitivity. The major serine protease expressed by neutrophils is neutrophil elastase (NE), which is inhibited endogenously by α1-antitrypsin A (A1AT). We investigated the effect of exogenous (A1AT) treatment on diet induced metabolic dysfunction. Male C57Bl/6j mice fed a chow or a high fat diet (HFD) were randomized to receive 3x weekly i.p injections of either Prolastin (human A1AT; 2mg) or vehicle (PBS) for 10 weeks. Prolastin treatment did not affect plasma NE concentration, body weight, glucose tolerance or insulin sensitivity in chow fed mice. In contrast, Prolastin treatment attenuated HFD induced increases in plasma and white adipose tissue (WAT) NE without affecting circulatory neutrophil levels or increases in body weight. Prolastin-treated mice fed a HFD had improved insulin sensitivity, as assessed by insulin tolerance test, and this was associated with higher insulin-dependent IRS-1 (insulin receptor substrate) and AktSer473phosphorylation, and reduced inflammation markers in WAT but not liver or muscle. In 3T3-L1 adipocytes, Prolastin reversed recombinant NE-induced impairment of insulin-stimulated glucose uptake and IRS-1 phosphorylation. Furthermore, PDGF mediated p-AktSer473 activation and glucose uptake (which is independent of IRS-1) was not affected by recombinant NE treatment. Collectively, our findings suggest that NE infiltration of WAT during metabolic overload contributes to insulin-resistance by impairing insulin-induced IRS-1 signaling.

The novel non‐steroidal MR antagonist finerenone improves metabolic parameters in high‐fat diet‐fed mice and activates brown adipose tissue via AMPK‐ATGL pathway

2020 ◽  
Vol 34 (9) ◽  
pp. 12450-12465 ◽  
Author(s):  
Vincenzo Marzolla ◽  
Alessandra Feraco ◽  
Stefania Gorini ◽  
Caterina Mammi ◽  
Carmen Marrese ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Metabolic Parameters ◽  
The Novel ◽  
High Fat ◽  
Brown Adipose

Defective trophic response of brown adipose tissue of myopathic hamsters

1984 ◽  
Vol 247 (6) ◽  
pp. E800-E807
Author(s):  
J. Triandafillou ◽  
W. Hellenbrand ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Muscular Dystrophy ◽  
Brown Adipose Tissue ◽  
Protein Content ◽  
High Fat Diet ◽  
Marked Reduction ◽  
Short Photoperiod ◽  
Normal Amount ◽  
High Fat ◽  
Brown Adipose

Hamsters with muscular dystrophy (BIO 14.6) have a smaller than normal amount of brown adipose tissue. Two stimuli that promote growth of brown adipose tissue in normal hamsters, short photoperiod and eating a high-fat diet, are here shown to be without effect on brown adipose tissue of myopathic hamsters. Cold-induced growth of brown adipose tissue occurs normally [Am. J. Physiol. 239 (Cell Physiol. 8): C18–C22, 1980]. There is a normal rate of turnover of norepinephrine in brown adipose tissue of the myopathic hamster but a failure of the tissue to hypertrophy in response to norepinephrine is unlikely since norepinephrine does not appear to mediate the trophic response [Am. J. Physiol. 247 (Endocrinol. Metab. 10): E793–E799, 1984]. Denervation results in a marked reduction in size (protein content) of brown adipose tissue of normal hamsters but has very little effect on the size of brown adipose tissue of myopathic hamsters. A central, possibly hypothalamic, defect in the myopathic hamster is postulated to underlie its abnormal control of brown adipose tissue hypertrophy.

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