Acetate alters expression of genes involved in beige adipogenesis in 3T3-L1 cells and obese KK-Ay mice

Abstract

The induction of beige adipogenesis within white adipose tissue, known as “browning”, has received attention as a novel potential anti-obesity strategy. The expression of some characteristic genes including PR domain containing 16 is induced during the browning process. Although acetate has been reported to suppress weight gain in both rodents and humans, its potential effects on beige adipogenesis in white adipose tissue have not been fully characterized. We examined the effects of acetate treatment on 3T3-L1 cells and in obese diabetic KK-Ay mice. The mRNA expression levels of genes involved in beige adipocyte differentiation and genes selectively expressed in beige adipocytes were significantly elevated in both 3T3-L1 cells incubated with 1.0 mM acetate and the visceral white adipose tissue from mice treated with 0.6% acetate for 16 weeks. In KK-Ay mice, acetate reduced the food efficiency ratio and increased the whole-body oxygen consumption rate. Additionally, reduction of adipocyte size and uncoupling protein 1-positive adipocytes and interstitial areas with multilocular adipocytes appeared in the visceral white adipose tissue of acetate-treated mice, suggesting that acetate induced initial changes of “browning”. In conclusion, acetate alters the expression of genes involved in beige adipogenesis and might represent a potential therapeutic agent to combat obesity.

Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota

“…Shotgun metagenomics sequencing analysis also showed that EODF upregulated the pathway of ‘Pyruvate fermentation to acetate and lactate by Lactobacillus reuteri ’ and ‘Pyruvate fermentation to acetate and lactate by unclassified bacteria’ (Figure S7). Intriguingly, recent studies indicate both acetate and lactate are beiging inducers (Hanatani et al, 2016; Kim et al, 2017; Sahuri-Arisoylu et al, 2016). In addition, both BAT and WAT express proton-linked monocarboxylate transporter 1 (MCT1) encoded by Mct1 , which drives acetate and lactate transport across the plasma membrane of adipocytes (den Besten et al, 2013; Iwanaga et al, 2009).…”

Gut Microbiota Interacts with Markers of Adipose Tissue Browning, Insulin Action and Plasma Acetate in Morbid Obesity

“…To explore the possible mechanism underlying the relationship between microbiota and adipose tissue browning, and considering the effects of circulating acetate on adipocyte browning and fat oxidation, its major abundance compared to other important gut microbial‐derived short‐chain fatty acids (propionate and butyrate), and its capacity to transfer from colon into bloodstream, circulating acetate levels in plasma were examined. Circulating acetate levels were significantly increased in insulin sensitive obese participants ( Figure a, Table ) in positive correlation with gut Firmicutes RA, SAT PRDM16 mRNA, and insulin sensitivity (Figure b–d), and negatively correlated with HOMA‐IR and fasting triglycerides (Figure e, f).…”

“…The mechanisms to explain the relationship between Ruminococcaceae RA and markers of browning in SAT remain to be elucidated. Gut microbial‐derived SCFAs have been demonstrated to improve insulin sensitivity through the enhancing of fat oxidation and energy expenditure . Acetate seems to exert a crucial role in brown adipocyte differentiation through the induction of mitochondrial biogenesis, leading to increased oxygen consumption rate in white and brown adipocytes and skeletal muscle from Otsuka Long‐Evans Tokushima Fatty rats; and increased browning of SAT in parallel to increased insulin sensitivity in mice .…”

“…Acetate seems to exert a crucial role in brown adipocyte differentiation through the induction of mitochondrial biogenesis, leading to increased oxygen consumption rate in white and brown adipocytes and skeletal muscle from Otsuka Long‐Evans Tokushima Fatty rats; and increased browning of SAT in parallel to increased insulin sensitivity in mice . Acetate administration also resulted in increased expression of browning genes (PRDM16, UCP1, and DIO2) in 3T3‐L1 cells and in white adipose tissue from obese diabetic KK‐A y mice in parallel to increased whole‐body oxygen consumption, leading to enhanced fat oxidation …”

Resveratrol liposomes and lipid nanocarriers: Comparison of characteristics and inducing browning of white adipocytes

“…We further studied browning effects of native R, R-nano, and R-lipo in differentiating 3T3-L1 white adipocytes, a commonly used cell model to study browning [27,28]. The hallmark of beige adipocytes is induced thermogenesis in response to stimuli, such as β-adrenergic agonist ISO.…”