scholarly journals Oxygenated Water Inhibits Adipogenesis and Attenuates Hepatic Steatosis in High-Fat Diet-Induced Obese Mice

2020 ◽  
Vol 21 (15) ◽  
pp. 5493
Author(s):  
Yuh-Jen Cheng ◽  
Chao-Chi Liu ◽  
Fang-Yeh Chu ◽  
Ching-Ping Yang ◽  
Chiao-Wan Hsiao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Hepatic Steatosis ◽  
Molecular Mechanisms ◽  
Metabolic Effects ◽  
Metabolic Function ◽  
Tissue Mass ◽  
Lipid Contents ◽  
Oxygenated Water

The expansion of adipose tissue mass is the primary characteristic of the process of becoming obesity, which causes chronic adipose inflammation and is closely associated with type 2 diabetes mellitus (T2DM). Adipocyte hypertrophy restricts oxygen availability, leading to microenvironmental hypoxia and adipose dysfunction. This study aimed at investigating the effects of oxygenated water (OW) on adipocyte differentiation (adipogenesis) and the metabolic function of mature adipocytes. The effects of OW on adipogenesis and the metabolic function of mature adipocytes were examined. Meanwhile, the in vivo metabolic effects of long-term OW consumption on diet-induced obesity (DIO) mice were investigated. OW inhibited adipogenesis and lipid accumulation through down-regulating critical adipogenic transcription factors and lipogenic enzymes. While body weight, blood and adipose parameters were not significantly improved by long-term OW consumption, transient circulatory triglyceride-lowering and glucose tolerance-improving effects were identified. Notably, hepatic lipid contents were significantly reduced, indicating that the DIO-induced hepatic steatosis was attenuated, despite no improvements in fibrosis and lipid contents in adipose tissue being observed in the OW-drinking DIO mice. The study provides evidence regarding OW’s effects on adipogenesis and mature adipocytes, and the corresponding molecular mechanisms. OW exhibits transient triglyceride-lowering and glucose tolerance-improving activity as well as hepatic steatosis-attenuating functions.

scholarly journals Epigallocatechin-3-Gallate Reduces Visceral Adiposity Partly through the Regulation of Beclin1-Dependent Autophagy in White Adipose Tissues

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3072
Author(s):  
Cheoljun Choi ◽  
Hyun-Doo Song ◽  
Yeonho Son ◽  
Yoon Keun Cho ◽  
Sang-Yeop Ahn ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
White Adipose Tissue ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Autophagic Flux ◽  
Tissue Mass ◽  
Egcg Treatment ◽  
Adipose Tissue Mass

Epigallocatechin-3-gallate (EGCG) is a primary bioactive phytochemical in green tea. Its therapeutic potential in metabolic diseases has been reported; however, the molecular mechanisms of the anti-obesity effect of EGCG have not been fully elucidated. In this study, we examined the effects of EGCG on lipid metabolism and autophagy in adipose tissue. After 8 weeks of high-fat diet feeding, mice were treated with EGCG (20 mg/kg/day) for 2 weeks to test in vivo anti-obesity effects of EGCG. EGCG treatment improved glucose tolerance and caused body weight loss. Interestingly, reduced adipose tissue mass was more prominent in visceral compared to subcutaneous white adipose tissue. Mechanistically, EGCG treatment increased autophagic flux in white adipose tissue through the AMP-activated protein kinase-mediated signaling pathway. Adipocyte-specific knockout of Beclin1 mitigated the effects of EGCG on visceral adipose tissue mass and glucose tolerance, indicating that the anti-obesity effect of EGCG requires Beclin1-dependent autophagy. Collectively, our data demonstrated that EGCG has anti-obesity effects through the upregulation of Beclin1-dependent autophagy and lipid catabolism in white adipose tissue (WAT).

KCTD10 regulates brown adipose tissue thermogenesis and metabolic function via Notch Signaling

2021 ◽  
Author(s):  
Mingsheng Ye ◽  
Liping Luo ◽  
Qi Guo ◽  
Guanghua Lei ◽  
Chao Zeng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Notch Signaling ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Notch Signaling Pathway ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Metabolic Function ◽  
Brown Adipose

Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 (PDIP1) family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 (UCP1) expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.

scholarly journals Thermoneutrality Reduces the Beneficial Metabolic Effects of Eicosapentaenoic Acid on White Adipose Tissue in Diet-Induced Obese Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1254-1254
Author(s):  
Bimba Goonapienuwala ◽  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
Kembra Albracht-Schulte ◽  
William Festuccia ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Eicosapentaenoic Acid ◽  
Uncoupling Protein ◽  
Serum Triglyceride ◽  
Metabolic Effects ◽  
Omega 3 ◽  
Adipocyte Size ◽  
Mitochondrial Energy Metabolism ◽  
Significant Difference

Abstract Objectives At ambient temperature (23°C), eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid reduces visceral adipose tissue (VAT) inflammation, adipocyte size and improves overall metabolic profile in diet-induced obese (DIO) mice, potentially through upregulation of uncoupling protein 1 (UCP-1). The goal of this study is to determine whether effects of EPA are maintained at thermoneutrality, and/or mediated by UCP-1, and if so through which cellular mechanisms. Methods Wild type (WT) and UCP-1 knockout (KO) B6 male mice were housed at thermoneutral temperature (28–30°C) and fed high fat (HF, 45% kcal fat) supplemented with or without EPA (36 g/kg diet). Serum, VAT (epididymal fat) and cecal microbiome specimens were analyzed. Results EPA reduced adiposity and improved glucose tolerance in EPA-fed KO mice (P < 0.05), but not in EPA-fed WT mice. EPA supplementation lowered VAT mass in both genotypes (P < 0.05); however, there were no diet or genotype-related differences in adipocyte size or serum triglyceride levels. Both genotypes fed EPA had lower serum resistin levels compared to respective HF (P < 0.01). EPA showed trends towards increased serum adiponectin levels compared to HF fed mice in both genotypes, with KO-EPA group having the highest concentration. There was no significant difference in the expression of IL-6 in VAT among the groups, while MCP-1 mRNA was expressed more in KO groups compared to WT groups (P < 0.01). Diet had no effect on expression of anti-inflammatory markers in both WT and KO mice. There were no genotype or diet effects on expression of genes involved in lipid metabolism and mitochondrial energy metabolism. Cecal microbiome showed no differences in the species diversity (Shannon index) between genotypes or diet types. However, only in the KO group, the Bacteroidetes/Firmicutes ratio was increased by EPA. Conclusions Compared to previous work at ambient temperatures, VAT does not mediate protective effects of EPA in DIO mice at thermoneutral temperature. Moreover, EPA effects are independent of UCP-1 as it produced beneficial effects on glucose tolerance and adiposity in KO mice, which may be in part mediated by changes in microbiome. Further mechanistic studies are ongoing to understand the mechanisms mediating EPA and UCP-1 effects in VAT. Funding Sources Funded by NIH (NCCIH and NIA).

TWEAK prevents TNF-α-induced insulin resistance through PP2A activation in human adipocytes

2013 ◽  
Vol 305 (1) ◽  
pp. E101-E112 ◽  
Author(s):  
Ana Vázquez-Carballo ◽  
Victòria Ceperuelo-Mallafré ◽  
Matilde R. Chacón ◽  
Elsa Maymó-Masip ◽  
Margarita Lorenzo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Signaling ◽  
Visceral Fat ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Metabolic Effects ◽  
Human Adipocytes ◽  
Fat Depots ◽  
Tnf Α

Visceral fat is strongly associated with insulin resistance. Obesity-associated adipose tissue inflammation and inflammatory cytokine production are considered key mediators of insulin signaling inhibition. TWEAK is a relatively new member of the TNF cytokine superfamily, which can exist as full length membrane-associated (mTWEAK) and soluble (sTWEAK) isoforms. Although TWEAK has been shown to have important functions in chronic inflammatory diseases its physiological role in adipose tissue remains unresolved. In this study, we explore the molecular mechanisms involved in the modulation of TNF-α-induced effects on insulin sensitivity by sTWEAK in a human visceral adipose cell line and also in primary human adipocytes obtained from visceral fat depots. Our data reveal that sTWEAK ameliorates TNF-α-induced insulin resistance on glucose uptake, GLUT4 translocation and insulin signaling without affecting other metabolic effects of TNF-α such as lipolysis or apoptotis. Co-immunoprecipitation experiments in adipose cells revealed that pretreatment with sTWEAK specifically inhibits TRAF2 association with TNFR1, but not with TNFR2, which mediates insulin resistance. However, sTWEAK does not affect other downstream molecules activated by TNF-α, such as TAK1. Rather, sTWEAK abolishes the stimulatory effect of TNF-α on JNK1/2, which is directly involved in the development of insulin resistance. This is associated with an increase in PP2A activity upon sTWEAK treatment. Silencing of the PP2A catalytic subunit gene overcomes the dephosphorylation effect of sTWEAK on JNK1/2, pointing to PP2A as a relevant mediator of sTWEAK-induced JNK inactivation. Overall, our data reveal a protective role of TWEAK in glucose homeostasis and identify PP2A as a new driver in the modulation of TNF-α signaling by sTWEAK.

scholarly journals Beneficial Metabolic Effects of TREM2 in Obesity are Uncoupled from its Expression on Macrophages

2021 ◽  
Author(s):  
Omar Sharif ◽  
Julia Stefanie Brunner ◽  
Ana Korosec ◽  
Rui Martins ◽  
Alexander Jais ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Immune Cell ◽  
Metabolic Effects ◽  
Sphingolipid Metabolism ◽  
Protective Effects ◽  
Tissue Macrophage ◽  
Insulin Tolerance ◽  
Ceramide Synthesis

Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass and hypercholesterolemia as hallmarks of unhealthy obesity, a recent report demonstrated ATM-expressed TREM2 promoted health. Here, we identified that in mice TREM2 deficiency aggravated diet-induced insulin resistance and hepatic steatosis independently of fat and cholesterol levels. Metabolomics linked TREM2 deficiency with elevated obesity-instigated serum ceramides that correlated with impaired insulin sensitivity. Remarkably, while inhibiting ceramide synthesis exerted no influences on TREM2-dependent ATM remodeling, inflammation or lipid load, it restored insulin tolerance, reversing adipose hypertrophy and secondary hepatic steatosis of TREM2-deficient animals. Bone marrow transplantation experiments revealed unremarkable influences of immune cell-expressed TREM2 on health instead demonstrating that WAT-intrinsic mechanisms impinging on sphingolipid metabolism dominate in TREM2’s systemic protective effects on metabolic health.

scholarly journals Brown adipose tissue prevents glucose intolerance and cardiac remodeling in high-fat-fed mice after a mild myocardial infarction

2021 ◽  
Author(s):  
Carmem Peres Valgas da Silva ◽  
Vikram K. Shettigar ◽  
Lisa A. Baer ◽  
Eaman Abay ◽  
Kendra L. Madaris ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Body Composition ◽  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Exercise Intolerance ◽  
Metabolic Function ◽  
High Fat ◽  
Brown Adipose

Abstract Background Obesity increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes (T2D) after myocardial infarction (MI). Brown adipose tissue (BAT) is important to combat obesity and T2D, and increasing BAT mass by transplantation improves glucose metabolism and cardiac function. The objective of this study was to determine if BAT had a protective effect on glucose tolerance and cardiac function in high-fat diet (HFD) fed mice subjected to a mild MI. Methods Male C57BL/6 mice were fed a HFD for eight weeks and then divided into Sham (Sham-operated) and +BAT (mice receiving 0.1 g BAT into their visceral cavity). Sixteen weeks post-transplantation, mice were further subdivided into ±MI (Sham; Sham-MI; +BAT; +BAT-MI) and maintained on a HFD. Cardiac (echocardiography) and metabolic function (glucose and insulin tolerance tests, body composition and exercise tolerance) were assessed throughout 22 weeks post-MI. Quantitative PCR (qPCR) was performed to determine the expression of genes related to metabolic function of perigonadal adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), liver, heart, tibialis anterior skeletal muscle (TA); and BAT. Results +BAT prevented the increase in left ventricle mass (LVM) and exercise intolerance in response to MI. Similar to what is observed in humans, Sham-MI mice developed IGT post-MI, but this was negated in +BAT-MI mice. IGT was independent of changes in body composition. Genes involved in inflammation, insulin resistance, and metabolism were significantly altered in pgWAT, scWAT, and liver in Sham-MI mice compared to all other groups. Conclusions BAT transplantation prevents IGT, the increase in LVM, and exercise intolerance following MI. MI alters the expression of several metabolic-related genes in WAT and liver in Sham-MI mice, suggesting that these tissues may contribute to the impaired metabolic response. Increasing BAT may be an important intervention to prevent the development of IGT or T2D and cardiac remodeling in obese patients post-MI.

scholarly journals Metabolic Effects of JAK1/2 Inhibition in Patients with Myeloproliferative Neoplasms

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Manali Sapre ◽  
Douglas Tremblay ◽  
Eric Wilck ◽  
Annie James ◽  
Amanda Leiter ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Myeloproliferative Neoplasms ◽  
Janus Kinase ◽  
Metabolic Effects ◽  
Baseline Body Mass Index ◽  
Single Center ◽  
Baseline Weight

Abstract Ruxolitinib is an FDA approved janus kinase (JAK)1/2 inhibitor used to treat myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera. We aimed to determine the metabolic consequences of ruxolitinib treatment in patients with MPNs. We performed a retrospective single-center cohort study utilizing an electronic medical record based database of patients who began treatment with ruxolitinib for MPNs from January 2010 to March 2017. We also examined the effects of ruxolitinib on adipose tissue JAK/STAT signaling in a mouse model. 127 patients were identified, of which 69 had data available for weight, and at least one other parameter of interest before, and 72 weeks after starting ruxolitinib. Mean baseline weight was 73.9 ± 17.0 kg, and 78.54 ± 19.1 kg at 72 weeks (p < 0.001). 50% of patients gained >5% body weight. Baseline body mass index (BMI) was 25.8 ± 4.8 kg/m2, and 27.5 ± 5.5 kg/m2 at 72 weeks (p < 0.001). Patients treated with ruxolitinib had a higher systolic blood pressure, serum AST, and ALT at 72 weeks, compared with baseline (p = 0.03, p = 0.01, p = 0.04, respectively). In mice, ruxolitinib decreased basal and GH-stimulated STAT5 phosphorylation in adipose tissue. As pharmacological JAK1/2 inhibitors are being developed and used in clinical practice, it is important to understand their long-term metabolic consequences.

scholarly journals The buckwheat iminosugar D-fagomine attenuates sucrose-induced steatosis and hypertension in rats

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Sara Ramos-Romero ◽  
Mercè Hereu ◽  
Lidia Atienza ◽  
Susana Amézqueta ◽  
Josefina Casas ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Uric Acid ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Visceral Fat ◽  
Molecular Mechanisms ◽  
Fat Deposition ◽  
Oral Glucose ◽  
Standard Diet

AbstractD-Fagomine (1,2 dideoxynojirimycin) is an iminosugar, a carbohydrate analogue that includes an endocyclic nitrogen instead of oxygen, that is naturally present in buckwheat and buckwheat-based foodstuffs. This study examines the long-term functional effect of d-fagomine on sucrose-induced factors of metabolic syndrome and explores possible molecular mechanisms behind its action. We evaluated Wistar Kyoto rats fed a standard diet were given a 35% sucrose (glucose/fructose) solution with d-fagomine (or not, for comparison) or mineral water (controls) for 24 weeks. The variables measured were body weight and energy intake; glucose tolerance (oral glucose tolerance test); plasma leptin concentration; plasma lipid profile; the populations of Bacteroidetes, Firmicutes, bacteroidales, clostridiales, enterobacteriales, and Escherichia coli in feces; blood pressure; urine uric acid and F2t isoprostanes (F2-IsoPs); perigonadal fat deposition and hepatic histology and diacylglycerols (DAGs) in liver and adipose tissue. We found that d-Fagomine reduced sucrose induced hypertension, urine uric acid, F2-IsoPs as markers of oxidative stress (OS), steatosis and liver DAGs (32:1, 32:2, 34:1 and 36:2) without affecting perigonadal (visceral) fat deposition or DAG levels in visceral adipose tissue. It showed a slight tendency to reduce sugar induced impaired glucose tolerance. d-Fagomine also promoted excretion of enterobacteriales generated by the dietary intervention. We postulate that fructose increases visceral fat deposition independently of liver de novo liposynthesis and that d-fagomine attenuates steatosis and blood pressure mainly by reducing liver fructose levels. The reduction of blood pressure may be associated with an effect on uric acid synthesis while the reduced levels of selected active liver DAGs may explain the weak effect on sucrose-induced impaired glucose tolerance, which may be primarily induced by visceral fat deposition. In conclusion, the increased populations of excreted enterobacteriales may be connected to the levels of excreted uric acid. d-Fagomine counteracts sucrose-induced steatosis and hypertension presumably by reducing the postprandial levels of fructose in the liver as a consequence of intestinal sucrase inhibition.

scholarly journals Glucocorticoid antagonism limits adiposity rebound and glucose intolerance in young male rats following the cessation of daily exercise and caloric restriction

2016 ◽  
Vol 311 (1) ◽  
pp. E56-E68 ◽  
Author(s):  
Trevor Teich ◽  
Emily C. Dunford ◽  
Deanna P. Porras ◽  
Jacklyn A. Pivovarov ◽  
Jacqueline L. Beaudry ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Receptor Antagonist ◽  
Caloric Restriction ◽  
Mass Gain ◽  
Male Rats ◽  
Tissue Mass ◽  
Adiposity Rebound ◽  
Adipose Tissue Mass

Severe caloric restriction (CR), in a setting of regular physical exercise, may be a stress that sets the stage for adiposity rebound and insulin resistance when the food restriction and exercise stop. In this study, we examined the effect of mifepristone, a glucocorticoid (GC) receptor antagonist, on limiting adipose tissue mass gain and preserving whole body insulin sensitivity following the cessation of daily running and CR. We calorically restricted male Sprague-Dawley rats and provided access to voluntary running wheels for 3 wk followed by locking of the wheels and reintroduction to ad libitum feeding with or without mifepristone (80 mg·kg−1·day−1) for 1 wk. Cessation of daily running and CR increased HOMA-IR and visceral adipose mass as well as glucose and insulin area under the curve during an oral glucose tolerance test vs. pre-wheel lock exercised rats and sedentary rats (all P < 0.05). Insulin sensitivity and glucose tolerance were preserved and adipose tissue mass gain was attenuated by daily mifepristone treatment during the post-wheel lock period. These findings suggest that following regular exercise and CR there are GC-induced mechanisms that promote adipose tissue mass gain and impaired metabolic control in healthy organisms and that this phenomenon can be inhibited by the GC receptor antagonist mifepristone.

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