Modulation of Adipocyte Metabolism by Microbial Short-Chain Fatty Acids
Abstract
:1. Introduction
2. SCFA Receptors and Obesity
2.1. Modulation of Obesity by SCFAs
2.2. Perturbation of SCFA Receptors: The Impact on Obesity
2.2.1. GPR41
2.2.2. GPR43
3. Direct Effects of Microbial-Derived SCFAs on Adipose Tissue
3.1. Microbial-Derived SCFA Effects on Energy Metabolism and Glucose Homeostasis
3.2. SCFAs and Lipolysis
3.3. SCFA Promote Adipogenesis and Browning of Adipose Tissue
3.4. SCFAs Modulate Adipose Tissue Inflammation
4. Indirect Effects of SCFAs on Adipose Tissue
4.1. Gut–Brain Axis Regulated by SCFAs
4.2. Gut–Liver SCFA Axis That Impacts Adipose Tissue
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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SCFA | Taxa | References | SCFA | Taxa | References |
---|---|---|---|---|---|
Acetate (C:2) | Bifidobacterium spp. Lactobacillus spp. Ruminococcus spp. Prevotella spp. Streptococcus spp. Bacteroides spp. Akkermancia muciniphila Escherichia coli | [53,54,55] | Butyrate (C:4) | Bifidobacterium spp. Eubacterium spp. Coprococcus spp. Roseburia spp. Bacteroides spp. Anaerostipes spp. Clostridium leptum Clostridium butyricum Butyrivibrio fibrisolvens Butyricicoccus pullicaecorum Faecalibacterium prausnitzii | [53,56,57,58,59,60,61,62,63] |
Propionate (C:3) | Bacteroides spp. Dialister spp. Veillonella spp. Salmonella spp. Lachnospiraceae spp. Megasphaera elsdenii Coprococcus cacus Roseburia inulinivorans Ruminococcus obeum Phascolarctobacterium succinatutens | [54,56,64,65] |
Experimental Design | Cell Type/Subject | Outcome | Study |
---|---|---|---|
Acetate given rectally (60 mM) or intravenously (20 mM), once weekly, for 4 weeks. | Hyperinsulinemic women (n = 6) | ↑ PYY, GLP-1 (rectal) ↓ TNF-α ↔ Adiponectin | Freeland et al. 2010 [137] |
WAT explants treated with 1–10 mM propionate for 24 h. | OAT and SAT explants from overweight women (n = 28) | ↑ Leptin mRNA ↓ Resistin mRNA | Al-Lahham et al. 2010 [127] |
WAT explants treated with 3 mM propionate for 24 h. | OAT explants from overweight women (n = 5) and THP-1 cells | ↑ LPL, GLUT4, SREBP-1c mRNA ↓ MMP-9, CD163, CD16A, CD31 mRNA Propionate blunts IL-4, IL-10, TNF-α, MIP-1α, MIP-β, CCL5. | Al-Lahham et al. 2012 [144] |
Intravenous acetate infusion (140 mM) for 90 min. | Men and women with (n = 3/6) or without (n = 4/5) hyperinsulinemia | ↑ serum acetate ↓ FFA | Fernandes et al. 2012 [145] |
10 g oral inulin-proionate ester (acute study). 10 g/day inulin-propionate ester for 24 weeks (chronic study). | Healthy men and women Acute effects (n = 15/5) Chronic effects (n = 60) | ↓ Energy intake, intra-abdominal adipose tissue distribution, body weight, intrahepatic cholesterol ↑ PYY, GLP-1 | Chambers et al. 2015 [129] |
Colonic infusion with 200 mM SCFA mixtures for 4 days. | Normoglycemic men (n = 12) | ↑ Energy expenditure, fat oxidation, PYY ↓ lipolysis | Canfora et al. 2017 [130] |
Colonic infusion with 180 mM acetate infusions for 3 days. | Overweight/obese men (n = 6) | ↑ Fasting fat oxidation, PYY, postprandial glucose and insulin | van der Beek et al. 2016 [136] |
1 μmol/L–1 mM single SCFA (acetate, propionate, butyrate) or SCFA mixtures for 6 h. | hMADS | ↓ Lipolysis, pHSL(SER650) ↑ GPR41 and GPR43 mRNA and protein | Jocken et al. 2017 [52] |
Plasma acetate measurement mRNA expression from WAT Fecal microbiota analyses | SAT and VAT explants from morbidly obese men and women (n = 6/28) | ↑ Plasma acetate, browning markers ↓ GLUT-4 mRNA | Moreno-Navarrete et al. 2018 [146] |
Oral delivery of butyrate (4 g/day) for 4 weeks | Healthy (n = 9) and metabolic syndrome men (n = 10) | ↑ Hepatic insulin sensitivity in lean subjects No effect on energy expenditure and plasma/fecal butyrate concentration | Bouter et al. 2018 [131] |
WAT explants treated with 3 mM propionate for 24 h | SAT explants from women (mean BMI = 28) (n = 10) | ↓ TNF-α, IL-10, CD163, MMP-9 ↑ RANTES↑ LPL, GLUT-4, SREBP-1c | Al-Lahham et al. 2019 [147] |
Experimental Design | Cell Type | Outcome | Study |
---|---|---|---|
1 μmol/L–1 mmol/L single SCFA (acetate, propionate, butyrate) or SCFA mixtures for 6 h. | hMADS | Acetate and SCFA mixtures high in acetate decreased lipolysis in basal human adipocytes. | Jocken et al., 2017 [52] |
0.1–0.3 mmol/L acetate and propionate for up to 4 h. | 3T3-L1, primary mouse adipocytes | Acetate and propionate inhibited lipolytic activity by approximately 50% in both cell types. | Ge et al., 2008 [53] |
0.1–1 mmol/L butyrate for 24 h. | 3T3-L1, RAW264.7 murine macrophages | Butyrate reduced lipolysis in co-cultured adipocytes in a dose-dependent manner. | Ohira et al., 2013 [55] |
20 mmol/L acetate or 5 mmol/L butyrate for up to 4 h. | 3T3-L1 | Both acetate and butyrate increased the rate of lipolysis in a dose-dependent manner. | Rumberger et al., 2014 [149] |
4 mM acetate for up to 2 h. | 3T3-L1 | Acetate decreased ISO-mediated lipolysis in adipocytes, mirrored by NEFA release in a time-dependent manner. | Aberdein et al., 2014 [116] |
3–10 mM acetate, propionate and butyrate for 10 min. | Primary human and rat adipocytes | Propionate and butyrate inhibited lipolysis in human adipocytes, whereas acetate exerted an antilipolytic effect in primary rat adipocytes. | Heimann et al., 2015 [151] |
0.01–0.1 μmol/L acetate and propionate for 7 days. | 3T3-L1 | Acetate and propionate blunted ISO-induced lipolysis in adipocytes, in a dose-dependent manner. | Hong et al. 2005 [78] |
Experimental Design | Cell or Tissue Type | Outcome | Study |
---|---|---|---|
5 mM butyrate for up to 7 days. | 3T3-L1 | ↑ Adipogenesis ↑ Lipid droplets ↑ LPL, aP2 mRNA expression | Toscani et al. 1990 [153] |
0.1–1.5 mM butyrate for up to 9 days. | Porcine stromal vascular | ↑ adipogenesis ↑ C/EBPα/β, PPAR-γ, SREBP-1c mRNA | Yan et al. 2015 [54] |
0.1–3 mM butyrate and propionate on day 10 of differentiation. | Porcine stromal vascular | ↑ Adipogenesis ↑ C/EBPα/β, PPAR-γ mRNA | Li et al. 2014 [50] |
6.4 mM acetate, 3.2 mM propionate, 0.8 mM butyrate for 10 days. | 3T3-L1 | ↑ Adipogenesis ↑ FAS, FATP4, aP2, LPL mRNA | Yu et al. 2018 [154] |
0.1 μmol/L acetate for 7 days. | 3T3-L1 | ↑ Adipogenesis ↑ PPAR-γ2 mRNA | Hong et al. 2005 [78] |
8 mM propionate and butyrate ~11 days. | SGBS | No effects on adipogenesis or adipogenic markers | Alex et al. 2013 [155] |
0.01–0.1 mM propionate for 8 days. | Broiler adipocytes | No effects on adipogenesis ↓ aP2, PPAR-γ mRNA | Li et al. 2021 [156] |
Plasma acetate measurement | SAT and VAT adipose tissue | ↑ Browning adipogenesis ↑ PRDM 16, UCP1, DIO2 mRNA | Moreno-Navarrete et al. 2018 [146] |
10 mM acetate for up to 7 days. | IM-BAT | ↑ Browning adipogenesis ↑ Mitochondrial biogenesis ↑ PGC-1α, PPAR-γ, aP2, UCP-1 mRNA | Hu et al. 2016 [84] |
1 mM acetate 0.6% acetate in drinking water for 16 weeks. | 3T3-L1 KK-Ay mice | ↑ Browning adipogenesis ↑ CIDEA, TMEM26, TBX1, FABP4, PPAR-γ, PRDM16, UCP-1, DIO2 mRNA | Hanatani et al. 2016 [51] |
5% wt wt−1 acetate, propionate, butyrate or mixture SCFA supplemented (3:1:1 ratio) in high-fat diet for 16 weeks. | C57Bl/6J mice | ↑ Browning adipogenesis ↑ PGC-1α, NRF-1, Tfam, β-F1 ATPase, COX IV, cyt-c | Lu et al. 2016 [17] |
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May, K.S.; den Hartigh, L.J. Modulation of Adipocyte Metabolism by Microbial Short-Chain Fatty Acids. Nutrients 2021, 13, 3666. https://doi.org/10.3390/nu13103666
May KS, den Hartigh LJ. Modulation of Adipocyte Metabolism by Microbial Short-Chain Fatty Acids. Nutrients. 2021; 13(10):3666. https://doi.org/10.3390/nu13103666
Chicago/Turabian StyleMay, Karolline S., and Laura J. den Hartigh. 2021. "Modulation of Adipocyte Metabolism by Microbial Short-Chain Fatty Acids" Nutrients 13, no. 10: 3666. https://doi.org/10.3390/nu13103666
APA StyleMay, K. S., & den Hartigh, L. J. (2021). Modulation of Adipocyte Metabolism by Microbial Short-Chain Fatty Acids. Nutrients, 13(10), 3666. https://doi.org/10.3390/nu13103666