The Experts below are selected from a list of 7761 Experts worldwide ranked by ideXlab platform
Johan W E Jocken - One of the best experts on this subject based on the ideXlab platform.
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short chain fatty acids differentially affect intracellular lipolysis in a human White Adipocyte model
Frontiers in Endocrinology, 2018Co-Authors: Johan W E Jocken, Manuel Gonzalez A Hernandez, Nicole T H Hoebers, Christina M Van Der Beek, Yvonne P G Essers, Ellen E Blaak, Emanuel E CanforaAbstract:Background & Aims: Gut-derived short-chain fatty acids (SCFA), formed by microbial fermentation of dietary fibres, are believed to be involved in the aetiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SCFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SCFA, we aimed to investigate the in vitro effects of SCFA incubations on intracellular lipolysis and signalling using a human White Adipocyte model, the hMADS cells. Methods: hMADS Adipocytes were incubated with mixtures of acetate, propionate and butyrate or single SCFA (acetate, propionate and butyrate) in concentrations ranging between 1 μmol/L and 1 mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following β-adrenergic stimulation. Results: SCFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P<0.05), whilst mixtures high in butyrate had no effect. Also, β-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SCFA mixtures. Incubation with only acetate decreased basal (1 μmol/L) and β-adrenergically (1 μmol/L and 1 mmol/L) mediated glycerol release as compared to control (P<0.05). In contrast, butyrate (1 μmol/L) slightly increased basal and β-adrenergically mediated glycerol release compared with control (P<0.05), whilst propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate. Conclusion: The present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SCFA and acts via attenuation of HSL phosphorylation in a Gi coupled manner in hMADS Adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism.
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Short-Chain Fatty Acids Differentially Affect Intracellular Lipolysis in a Human White Adipocyte Model
Frontiers Media S.A., 2018Co-Authors: Johan W E Jocken, Manuel Gonzalez A Hernandez, Nicole T H Hoebers, Christina M Van Der Beek, Yvonne P G Essers, Ellen E Blaak, Emanuel E CanforaAbstract:Background and aimsGut-derived short-chain fatty acids (SCFA), formed by microbial fermentation of dietary fibers, are believed to be involved in the etiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SCFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SCFA, we aimed to investigate the in vitro effects of SCFA incubations on intracellular lipolysis and signaling using a human White Adipocyte model, the human multipotent adipose tissue-derived stem (hMADS) cells.MethodshMADS Adipocytes were incubated with mixtures of acetate, propionate, and butyrate or single SCFA (acetate, propionate and butyrate) in concentrations ranging between 1 µmol/L and 1 mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following β-adrenergic stimulation.ResultsSCFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P < 0.05), while mixtures high in butyrate had no effect. Also, β-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SCFA mixtures. Incubation with only acetate decreased basal (1 µmol/L) and β-adrenergically (1 µmol/L and 1 mmol/L) mediated glycerol release when compared with control (P < 0.05). In contrast, butyrate (1 µmol/L) slightly increased basal and β-adrenergically mediated glycerol release compared with control (P < 0.05), while propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone-sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate.ConclusionThe present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SCFA and acts via attenuation of HSL phosphorylation in a Gi-coupled manner in hMADS Adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism
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combinations of bio active dietary constituents affect human White Adipocyte function in vitro
Nutrition & Metabolism, 2016Co-Authors: Ines Warnke, Johan W E Jocken, Rotraut Schoop, Christine Toepfer, Regina Goralczyk, Joseph SchwagerAbstract:Background Specific bio-active dietary compounds modulate numerous metabolic processes in adipose tissue (AT), including pre-Adipocyte proliferation and differentiation. AT dysfunction, rather than an increased fat mass per se, is strongly associated with the development of insulin resistance and is characterized by impaired adipogenesis, hypertrophic Adipocytes, inflammation, and impairments in substrate metabolism. A better understanding of mechanisms underlying AT dysfunction may provide new strategies for the treatment of obesity-associated metabolic diseases. Here we evaluated the role of (all-E)-lycopene (Lyc), eicosapentaenoic acid (EPA) or trans-resveratrol (Res) and combinations thereof on human White Adipocyte function.
Emanuel E Canfora - One of the best experts on this subject based on the ideXlab platform.
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short chain fatty acids differentially affect intracellular lipolysis in a human White Adipocyte model
Frontiers in Endocrinology, 2018Co-Authors: Johan W E Jocken, Manuel Gonzalez A Hernandez, Nicole T H Hoebers, Christina M Van Der Beek, Yvonne P G Essers, Ellen E Blaak, Emanuel E CanforaAbstract:Background & Aims: Gut-derived short-chain fatty acids (SCFA), formed by microbial fermentation of dietary fibres, are believed to be involved in the aetiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SCFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SCFA, we aimed to investigate the in vitro effects of SCFA incubations on intracellular lipolysis and signalling using a human White Adipocyte model, the hMADS cells. Methods: hMADS Adipocytes were incubated with mixtures of acetate, propionate and butyrate or single SCFA (acetate, propionate and butyrate) in concentrations ranging between 1 μmol/L and 1 mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following β-adrenergic stimulation. Results: SCFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P<0.05), whilst mixtures high in butyrate had no effect. Also, β-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SCFA mixtures. Incubation with only acetate decreased basal (1 μmol/L) and β-adrenergically (1 μmol/L and 1 mmol/L) mediated glycerol release as compared to control (P<0.05). In contrast, butyrate (1 μmol/L) slightly increased basal and β-adrenergically mediated glycerol release compared with control (P<0.05), whilst propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate. Conclusion: The present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SCFA and acts via attenuation of HSL phosphorylation in a Gi coupled manner in hMADS Adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism.
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Short-Chain Fatty Acids Differentially Affect Intracellular Lipolysis in a Human White Adipocyte Model
Frontiers Media S.A., 2018Co-Authors: Johan W E Jocken, Manuel Gonzalez A Hernandez, Nicole T H Hoebers, Christina M Van Der Beek, Yvonne P G Essers, Ellen E Blaak, Emanuel E CanforaAbstract:Background and aimsGut-derived short-chain fatty acids (SCFA), formed by microbial fermentation of dietary fibers, are believed to be involved in the etiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SCFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SCFA, we aimed to investigate the in vitro effects of SCFA incubations on intracellular lipolysis and signaling using a human White Adipocyte model, the human multipotent adipose tissue-derived stem (hMADS) cells.MethodshMADS Adipocytes were incubated with mixtures of acetate, propionate, and butyrate or single SCFA (acetate, propionate and butyrate) in concentrations ranging between 1 µmol/L and 1 mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following β-adrenergic stimulation.ResultsSCFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P < 0.05), while mixtures high in butyrate had no effect. Also, β-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SCFA mixtures. Incubation with only acetate decreased basal (1 µmol/L) and β-adrenergically (1 µmol/L and 1 mmol/L) mediated glycerol release when compared with control (P < 0.05). In contrast, butyrate (1 µmol/L) slightly increased basal and β-adrenergically mediated glycerol release compared with control (P < 0.05), while propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone-sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate.ConclusionThe present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SCFA and acts via attenuation of HSL phosphorylation in a Gi-coupled manner in hMADS Adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism
Emmanuelle Havis - One of the best experts on this subject based on the ideXlab platform.
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Egr1 deficiency induces browning of inguinal subcutaneous White adipose tissue in mice.
Scientific reports, 2017Co-Authors: Cécile Milet, Delphine Duprez, Marianne Bleher, Kassandra Allbright, Mickael Orgeur, Fanny Coulpier, Emmanuelle HavisAbstract:Beige Adipocyte differentiation within White adipose tissue, referred to as browning, is seen as a possible mechanism for increasing energy expenditure. The molecular regulation underlying the thermogenic browning process has not been entirely elucidated. Here, we identify the zinc finger transcription factor EGR1 as a negative regulator of the beige fat program. Loss of Egr1 in mice promotes browning in the absence of external stimulation and leads to an increase of Ucp1 expression, which encodes the key thermogenic mitochondrial uncoupling protein-1. Moreover, EGR1 is recruited to the proximal region of the Ucp1 promoter in subcutaneous inguinal White adipose tissue. Transcriptomic analysis of subcutaneous inguinal White adipose tissue in the absence of Egr1 identifies the molecular signature of White Adipocyte browning downstream of Egr1 deletion and highlights a concomitant increase of beige differentiation marker and a decrease in extracellular matrix gene expression. Conversely, Egr1 overexpression in mesenchymal stem cells decreases beige Adipocyte differentiation, while increasing extracellular matrix production. These results reveal a role for Egr1 in blocking energy expenditure via direct Ucp1 transcription repression and highlight Egr1 as a therapeutic target for counteracting obesity.
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Egr1 deficiency induces browning of inguinal subcutaneous White adipose tissue in mice
2017Co-Authors: Cécile Milet, Delphine Duprez, Marianne Bleher, Kassandra Allbright, Mickael Orgeur, Fanny Coulpier, Emmanuelle HavisAbstract:Beige Adipocyte differentiation within White adipose tissue, referred to as browning, is seen as a possible mechanism for increasing energy expenditure. The molecular regulation underlying the thermogenic browning process has not been entirely elucidated. Here, we identify the zinc finger transcription factor EGR1 as a negative regulator of the beige fat program. Loss of Egr1 in mice promotes browning in the absence of external stimulation and activates Ucp1 that encodes the key thermogenic mitochondrial uncoupling protein-1. Moreover, EGR1 is recruited to the proximal region of the Ucp1 promoter in subcutaneous inguinal White adipose tissue. Transcriptomic analysis of subcutaneous inguinal White adipose tissue in the absence of Egr1 identifies the molecular signature of White Adipocyte browning downstream of Egr1 deletion and highlights a concomitant increase of beige differentiation marker and decrease in extracellular matrix gene expression. Conversely, Egr1 overexpression in mesenchymal stem cells decreases beige Adipocyte differentiation, while increasing extracellular matrix production. These results uncover the role of Egr1 in blocking energy expenditure via direct Ucp1 transcription regulation and highlight Egr1 as a therapeutic target for counteracting obesity.
Silke S Heinzmann - One of the best experts on this subject based on the ideXlab platform.
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asc 1 regulates White versus beige Adipocyte fate in a subcutaneous stromal cell population
Nature Communications, 2021Co-Authors: Lisa Suwandhi, Irem Altun, Ruth Karlina, Viktorian Miok, Tobias Wiedemann, David S Fischer, Thomas Walzthoeni, Christina Lindner, Anika Bottcher, Silke S HeinzmannAbstract:Adipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, White adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preAdipocytes expressing the mature White Adipocyte marker Asc-1 that showed a low ability to differentiate into beige Adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preAdipocytes resulted in spontaneous differentiation of beige Adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preAdipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine. Adipose tissue is composed of a variety of cell types, including Adipocyte precursor populations, that contribute to adipose tissue function upon differentiation. Here, using scRNA-sequencing of adolescent and adult mouse subcutaneous adipose tissue, the authors identify an Asc-1 positive preAdipocyte population that is enriched in adolescent subcutaneous fat and demonstrate that loss of Asc-1 triggers spontaneous beige Adipocyte differentiation.
William L. Holland - One of the best experts on this subject based on the ideXlab platform.
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directing visceral White Adipocyte precursors to a thermogenic Adipocyte fate improves insulin sensitivity in obese mice
eLife, 2017Co-Authors: Chelsea Hepler, Mengle Shao, Lavanya Vishvanath, William L. Holland, Jonathan Y Xia, Alexandra L Ghaben, Mackenzie J Pearson, Ankit X Sharma, Thomas S Morley, Rana K GuptaAbstract:Mammals have different types of fat cells in their bodies. White fat cells store energy for later use, and brown and beige fat cells burn energy to help keep the body warm. Individuals who are obese typically have too many White fat cells in and around their belly. This belly fat, also called visceral fat, accumulates around the organs and is believed to contribute to metabolic diseases, such as diabetes and heart disease. Individuals who are obese also have relatively few brown and beige energy-burning fat cells. Boosting the amount of brown and beige fat in individuals who are obese has been proposed as a potential way to reduce their risk of metabolic disease. One way to do this would be to encourage White visceral fat cells to become more like energy-burning beige or brown fat cells. Recent research has shown that White fat cells contain higher amounts of a protein called Zfp423 than brown or beige fat cells. This protein turns off the genes that fat cells use to burn energy and so keeps White fat cells in an energy-storing state. Now, Hepler et al. show that genetically modifying mice to turn off the gene that produces Zfp423 specifically in the precursor cells that become White fat cells causes more energy-burning beige cells to appear in their visceral fat. The genetically modified mice were better able to tolerate cold than normal mice. When placed on a high-fat diet, the modified mice were also less likely to become resistant to the effects of the hormone insulin – a process that can lead to the development of type 2 diabetes and may be linked to heart disease. This suggests that treatments that prevent Zfp423 from working in fat cells could help to treat or prevent diabetes and heart disease in people who are obese. Before such treatments can be developed, further work is needed to investigate how Zfp423 works in more detail, and to confirm that it has the same effects in human fat cells as it does in mice.
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Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program
Cell Metabolism, 2016Co-Authors: Mengle Shao, Jeff Ishibashi, Christine M. Kusminski, Qiong A. Wang, Chelsea Hepler, Lavanya Vishvanath, Karen A. Macpherson, Stephen B. Spurgin, Kai Sun, William L. HollandAbstract:The transcriptional regulators Ebf2 and Prdm16 establish and maintain the brown and/or beige fat cell identity. However, the mechanisms operating in White Adipocytes to suppress the thermogenic gene program and maintain an energy-storing phenotype are less understood. Here, we report that the transcriptional regulator Zfp423 is critical for maintaining White Adipocyte identity through suppression of the thermogenic gene program. Zfp423 expression is enriched in White versus brown Adipocytes and suppressed upon cold exposure. Doxycycline-inducible inactivation of Zfp423 in mature Adipocytes, combined with β-adrenergic stimulation, triggers a conversion of differentiated adiponectin-expressing inguinal and gonadal Adipocytes into beige-like Adipocytes; this reprogramming event is sufficient to prevent and reverse diet-induced obesity and insulin resistance. Mechanistically, Zfp423 acts in Adipocytes to inhibit the activity of Ebf2 and suppress Prdm16 activation. These data identify Zfp423 as a molecular brake on Adipocyte thermogenesis and suggest a therapeutic strategy to unlock the thermogenic potential of White Adipocytes in obesity.
