Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice

Sakakibara, Shoji; Yamauchi, Toshimasa; Oshima, Yoshifumi; Tsukamoto, Yoshinori; Kadowaki, Takashi

doi:10.1016/j.bbrc.2006.03.176

Cited by 208 publications

(168 citation statements)

References 28 publications

Supporting

Mentioning

148

Contrasting

Unclassified

Order By: Relevance

“…Modifications in the gut microbiota profile promoted by antibiotic therapy induced an increase in the portal levels of circulating acetate. Acetate has the capacity to activate AMPK in liver and muscle [31], increasing fatty acid oxidation [32]. In a corroborative way, we showed that after oral administration and venous infusion of acetate in mice, phosphorylation of AMPK and ACC was increased.…”

Section: Discussionsupporting

confidence: 64%

Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice

et al. 2012

View full text Add to dashboard Cite

Aims/hypothesis A high-fat dietary intake induces obesity and subclinical inflammation, which play important roles in insulin resistance. Recent studies have suggested that increased concentrations of circulating lipopolysaccharide (LPS), promoted by changes in intestinal permeability, may have a pivotal role in insulin resistance. Thus, we investigated the effect of gut microbiota modulation on insulin resistance and macrophage infiltration. Methods Swiss mice were submitted to a high-fat diet with antibiotics or pair-feeding for 8 weeks. Metagenome analyses were performed on DNA samples from mouse faeces. Blood was collected to determine levels of glucose, insulin, LPS, cytokines and acetate. Liver, muscle and adipose tissue proteins were analysed by western blotting. In addition, liver and adipose tissue were analysed, blinded, using histology and immunohistochemistry. Results Antibiotic treatment greatly modified the gut microbiota, reducing levels of Bacteroidetes and Firmicutes, overall bacterial count and circulating LPS levels. This modulation reduced levels of fasting glucose, insulin, TNF-α and IL-6; reduced activation of toll-like receptor 4 (TLR4), c-Jun N-terminal kinase (JNK), inhibitor of κ light polypeptide gene enhancer in B cells, kinase β (IKKβ) and phosphorylated IRS-1 Ser307; and consequently improved glucose tolerance and insulin tolerance and action in metabolically active tissues. In addition, there was an increase in portal levels of circulating acetate, which probably contributed to an increase in 5′-AMP-activated protein kinase (AMPK) phosphorylation in mice. We observed a striking reduction in crown-like structures (CLS) and F4/80 + macrophage cells in the adipose tissue of antibiotic-treated mice. Conclusions/interpretation These results suggest that modulation of gut microbiota in obesity can improve insulin signalling and glucose tolerance by reducing circulating LPS levels and inflammatory signalling. Modulation also appears to increase levels of circulating acetate, which activates AMPK and finally leads to reduced macrophage infiltration.

show abstract

Section: Discussionsupporting

confidence: 64%

Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Acetic acid reduced the expression of genes involved in gluconeogenesis and lipogenesis, which is partially regulated by AMPK. They also reported that sodium acetate, in the form of neutralized AcOH, directly activated AMPK and lowered the expression of genes such as for glucose-6-phosphatase (Sakakibara et al 2006). These results indicate that the Table 3.…”

Section: Discussionmentioning

confidence: 98%

“…Sakakibara et al (2006) revealed the efficacy of acetic acid on reducing fasting plasma glucose level and hemoglobin A1c by giving mice 0.3% acetic acid for 8 weeks. Acetic acid reduced the expression of genes involved in gluconeogenesis and lipogenesis, which is partially regulated by AMPK.…”

Section: Discussionmentioning

confidence: 99%

Intake of Vinegar Beverage Is Associated with Restoration of Ovulatory Function in Women with Polycystic Ovary Syndrome

Kimura

Takashima

et al. 2013

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is one of major causes of irregular menstruation. It is defined as a condition involving the combination of hyperandrogenism and chronic oligomenorrhea or anovulation, and is thought to have a variety of etiologies. Insulin resistance (impaired insulin sensitivity) has been suggested to be one of the etiologies of PCOS. PCOS patients often need to take medication to treat anovulation and infertility. Therefore, it would be beneficial to patients if simple non-pharmacological treatments can be developed. Recently the efficacy of vinegar to improve insulin resistance has been reported. To study the effect of vinegar on metabolic and hormonal indices and ovulatory function in PCOS, seven patients seeking a non-pharmacological treatment for PCOS took a beverage containing 15 g of apple vinegar daily for 90 to 110 days. Ovulation, the menstrual interval, fasting serum glucose level, fasting serum insulin level, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone were compared before and after intake of the vinegar beverage. Intake of the vinegar beverage resulted in a decrease of the homeostasis model assessment insulin resistance index (HOMA-R) in six patients, as well as a decrease of the LH/FSH ratio in five of seven patients. Ovulatory menstruation was observed within 40 day in four of seven patients. These findings suggest the possibility of vinegar to restore ovulatory function through improving insulin sensitivity in PCOS patients, thus, avoiding pharmacological treatment. Intake of vinegar might reduce medical cost and treatment time for insulin resistance, anovulation, and infertility in patients with PCOS.

show abstract

“…PGC-1α in turn regulates several transcriptional factors such as peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, PPAR-δ, and farnesoid X receptor (FXR), all of which regulate glucose-, lipid-, and cholesterol metabolism [42][43][44][45][46]. Furthermore, AMPK activation reduces hepatic expression of genes involved in gluconeogenesis, like glucose-6-phosphatase [46]. Interestingly, both PPARα and PPARγ have been used as pharmaceutical substrates for lipid-lowering (fibrates) and insulinsensitizing (thiazolidinediones) drugs.…”

Section: Glucose Metabolismmentioning

confidence: 99%

The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids

Fluitman

Clercq

Keijser

et al. 2017

Expert Review of Endocrinology & Metabolism

View full text Add to dashboard Cite

Introduction: Malnutrition refers to both over-and undernutrition and results from a disruption in energy balance. It affects one in three people worldwide and is associated with increased morbidity and mortality. The intestinal microbiota represents a newly identified factor that might contribute to the development of malnutrition, as it harbors traits that complement the human metabolic and endocrine capabilities, thereby influencing energy balance. Areas covered: In the current review, we aim to give a comprehensive overview on the microbiota, its development and its possible influence on energy balance, with emphasis the role of short-chain fatty acids. We also consider microbial characteristics associated with obesity and undernutrition and evaluate microbial manipulating strategies. The PubMed database was searched using the terms:

show abstract

Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice

Cited by 208 publications

References 28 publications

Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice

Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice

Intake of Vinegar Beverage Is Associated with Restoration of Ovulatory Function in Women with Polycystic Ovary Syndrome

The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids

Contact Info

Product

Resources

About