Gamma-Aminobutyric Acid Signaling in Brown Adipose Tissue Promotes Systemic Metabolic Derangement in Obesity

Ikegami, Ryutaro; Shimizu, Ippei; Satô, Takeshi; Yoshida, Yohko; Hayashi, Yuka; Suda, Masayoshi; Katsuumi, Goro; Li, Ji; Wakasugi, Tatsuya; Minokoshi, Yasuhiko; Okamoto, Susumu; Hinoi, Eiichi; Nielsen, Søren; Jespersen, Naja Zenius; Schéele, Camilla; Soga, Tomoyoshi; Minamino, Tohru

doi:10.1016/j.celrep.2018.08.024

Cited by 43 publications

(25 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been recently reported that GABA might be involved in the regulation of obesity and energy metabolism (43,(53)(54)(55). In pro-opiomelanocortin neurons, GABA B receptor ablation results in increased obesity and insulin resistance via dysregulation of the appetite (53).…”

Section: Discussionmentioning

confidence: 99%

GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity

Hwang

Shin

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Accumulating evidence suggests that subcutaneous and visceral adipose tissues are differentially associated with metabolic disorders. In obesity, subcutaneous adipose tissue is beneficial for metabolic homeostasis because of repressed inflammation. However, the underlying mechanism remains unclear. Here, we demonstrate that γ-aminobutyric acid (GABA) sensitivity is crucial in determining fat depot-selective adipose tissue macrophage (ATM) infiltration in obesity. In diet-induced obesity, GABA reduced monocyte migration in subcutaneous inguinal adipose tissue (IAT), but not in visceral epididymal adipose tissue (EAT). Pharmacological modulation of the GABAB receptor affected the levels of ATM infiltration and adipose tissue inflammation in IAT, but not in EAT, and GABA administration ameliorated systemic insulin resistance and enhanced insulin-dependent glucose uptake in IAT, accompanied by lower inflammatory responses. Intriguingly, compared with adipose-derived stem cells (ADSCs) from EAT, IAT-ADSCs played key roles in mediating GABA responses that repressed ATM infiltration in high-fat diet-fed mice. These data suggest that selective GABA responses in IAT contribute to fat depot-selective suppression of inflammatory responses and protection from insulin resistance in obesity.

show abstract

Section: Discussionmentioning

confidence: 99%

GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity

Hwang

Shin

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Moreover, in experimental animals, high fat diet leads to a chronic up-regulation of the GABA-BR1 in adipose tissue and its translocation into cellular membrane, making adipocytes of obese animals more sensitive to the damaging effects of GABA. In turn, suppression of excessive signaling by the inhibition of mitochondrial calcium overload restores normal BAT function [ 40 ].…”

Section: Adipose Tissue Browningmentioning

confidence: 99%

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Kuryłowicz

Puzianowska-Kuźnicka

2020

IJMS

148

View full text Add to dashboard Cite

The ongoing obesity pandemic generates a constant need to develop new therapeutic strategies to restore the energy balance. Therefore, the concept of activating brown adipose tissue (BAT) in order to increase energy expenditure has been revived. In mammals, two developmentally distinct types of brown adipocytes exist; the classical or constitutive BAT that arises during embryogenesis, and the beige adipose tissue that is recruited postnatally within white adipose tissue (WAT) in the process called browning. Research of recent years has significantly increased our understanding of the mechanisms involved in BAT activation and WAT browning. They also allowed for the identification of critical molecules and critical steps of both processes and, therefore, many new therapeutic targets. Several non-pharmacological approaches, as well as chemical compounds aiming at the induction of WAT browning and BAT activation, have been tested in vitro as well as in animal models of genetically determined and/or diet-induced obesity. The therapeutic potential of some of these strategies has also been tested in humans. In this review, we summarize present concepts regarding potential therapeutic targets in the process of BAT activation and WAT browning and available strategies aiming at them.

show abstract

“…More recently, it has been shown that HFD increases UCP1 thermogenic protein in mice and rats [115,116] and BAT temperature after 20 weeks of diet [117]. Importantly, it has been demonstrated that the levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that suppresses neuron excitability, are increased in BAT of HFD-fed mice promoting BAT disfunction [118]. All these exiting results provide new insights into innervation patterns and nerve plasticity in adipose depots, suggesting that neuromodulation could become an essential strategy to explore new ways to treat obesity (reviewed in [119][120][121][122]).…”

Section: Physiological Mechanisms Involved In Diet-induced Obesitymentioning

confidence: 99%

Dietary Options for Rodents in the Study of Obesity

2020

View full text Add to dashboard Cite

Obesity and its associated metabolic diseases are currently a priority research area. The increase in global prevalence at different ages is having an enormous economic and health impact. Genetic and environmental factors play a crucial role in the development of obesity, and diet is one of the main factors that contributes directly to the obesogenic phenotype. Scientific evidence has shown that increased fat intake is associated with the increase in body weight that triggers obesity. Rodent animal models have been extremely useful in the study of obesity since weight gain can easily be induced with a high-fat diet. Here, we review the dietary patterns and physiological mechanisms involved in the dynamics of energy balance. We report the main dietary options for the study of obesity and the variables to consider in the use of a high-fat diet, and assess the progression of obesity and diet-induced thermogenesis.

show abstract

Gamma-Aminobutyric Acid Signaling in Brown Adipose Tissue Promotes Systemic Metabolic Derangement in Obesity

Cited by 43 publications

References 41 publications

GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity

GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Dietary Options for Rodents in the Study of Obesity

Contact Info

Product

Resources

About