Allicin ameliorates obesity comorbid depressive-like behaviors: involvement of the oxidative stress, mitochondrial function, autophagy, insulin resistance and NOX/Nrf2 imbalance in mice

Abstract

The increased prevalence of obesity has been a major medical and public health problem in the past decades. In obese status, insulin resistance and sustained oxidative stress damage might give rise to behavioral deficits. The anti-obesity and anti-oxidant effects of allicin have been previously reported in peripheral tissues. In the present study, the functions and mechanisms of allicin involved in the prevention of high-fat diet (HFD)-induced depressive-like behaviors were investigated to better understand the pharmacological activities of allicin. Obese mice (five weeks of age) were treated with allicin (50, 100, and 200 mg/kg) by gavage for 15 weeks and behavioral test (sucrose preference, open field, and tail suspension) were performed. Furthermore, markers of oxidative stress, mitochondrial function, autophagy, and insulin resistance were measured in the hippocampal tissue. Finally, the levels of NADPH oxidase (NOX2, NOX4) and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway were evaluated in the hippocampus. The body weight, metabolic disorders, and depressive-like behaviors in obese mice were ameliorated by allicin. The depressive-like behaviors presented in the obese mice were accompanied by remarkably excessive reactive oxygen species (ROS) production and oxidative stress, damaged mitochondrial function, imbalanced autophagy, and enhanced insulin resistance in the hippocampus. We found that allicin improved the above undesirable effects in the obese mice. Furthermore, allicin significantly decreased NOX2 and NOX4 levels and activated the Nrf2 pathway. Allicin attenuated depressive-like behaviors triggered by long-term HFD consumption by inhibiting ROS production and oxidative stress, improving mitochondrial function, regulating autophagy, and reducing insulin resistance in the hippocampus via optimization of NOX/Nrf2 imbalance.

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Abbreviations

HFD:

High fat diet

FER:

Food efficiency ratio

SPT:

Sucrose preference test

OFT:

Open field test

TST:

Tail suspension test

ROS:

Reactive oxygen species

MDA:

Malonaldehyde

SOD:

Superoxide dismutase

CAT:

Catalase

GSH:

Glutathione

GPx:

Glutathion peroxidase

ATG 5:

Autophagy-related protein 5

LC3B:

Microtubule-associated protein light chain 3B

Nrf2:

Nuclear factor erythroid 2-related factor 2

HO-1:

Heme oxygenase-1

NOX:

NADPH oxidase

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National Natural Science Foundation of China, the grant number are 81470387 and 81500230.

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Correspondence to Jian Yang or Zhifang Deng.

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Gao, W., Wang, W., Zhang, J. et al. Allicin ameliorates obesity comorbid depressive-like behaviors: involvement of the oxidative stress, mitochondrial function, autophagy, insulin resistance and NOX/Nrf2 imbalance in mice. Metab Brain Dis 34, 1267–1280 (2019). https://doi.org/10.1007/s11011-019-00443-y

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Keywords

  • Obesity
  • Depressive-like behaviors
  • NADPH oxidase
  • Nrf2