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Metformin Reduces Lipogenesis Markers in Obese Mice Fed a Low-Carbohydrate and High-Fat Diet

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Lipids

Abstract

Lipogenesis is the process by which fatty acids are synthesized. In metabolic syndrome, an insulin resistant state along with high plasma levels of free fatty acids (FFA) and hyperglycemia may contribute to the lipogenic process. The aim of the present study was to investigate the effects of oral administration of metformin on the expression of lipogenic genes and glycemic profile in mice fed with low-carbohydrate high-fat diet by evaluating their metabolic profile. SWISS male mice were divided into 4 groups (N = 7) that were fed with standard (ST), standard plus metformin (ST + MET), low-carbohydrate high-fat diet (LCHFD) and low-carbohydrate high-fat diet plus metformin (LCHFD + MET) (100 mg kg−1 diet) diets respectively. Food intake, body weight and blood parameters, such as glucose tolerance, insulin sensitivity, glucose, HDL-c, total cholesterol, triglycerides, ASL and ALT levels were assessed. Histological analyses were performed on hematoxylin and eosin-stained epididymal adipose tissue histological specimens. The expression levels of peroxisome proliferator-activated receptor (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), were assessed by RT-PCR. This study showed that metformin decreased adipocyte area, body weight and food consumption in obese animals when compared to the standard group. Furthermore, the expression of lipogenic markers in adipose tissue were diminished in obese animals treated with metformin. This data showed that oral administration of metformin improved glucose and lipid metabolic parameters in white adipose tissue by reducing the expression of lipogenesis markers, suggesting an important clinical application of MET in treating obesity-related diseases in metabolic syndrome.

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Abbreviations

ACC:

Acetyl CoA carboxylase

AMPK:

AMP-activated protein kinase

FAS:

Fatty acid synthase

FFA:

Free fat acids

GAPDH:

Glyceraldehyde 3- phosphate dehydrogenase

HDL:

High-density lipoprotein

LCHFD:

Low-carbohydrate high-fat diet

LCHFD + MET:

Low-carbohydrate high-fat diet plus metformin

H&E:

Hematoxylin and eosin

LDL:

Low-density lipoprotein

MetS:

Metabolic syndrome

PPARγ:

Peroxisome proliferator-activated receptor

qRT-PCR:

Real time PCR

SREBP-1:

Protein-1 sterol regulatory element binding

ST:

Standard diet

VLDL:

Very low-density lipoprotein

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Financial support

This work was partially supported by the Coordenadoria de Aperfeiçoamento do Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG).

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Authors and Affiliations

  1. Laboratory of Health Science, Postgraduate Program in Health Sciences, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, MG, Brazil

    Karla Nayara de Oliveira Santana, Deborah Farias Lelis, Keila Lopes Mendes, Jamille Fernandes Lula, Alanna Fernandes Paraíso, João Marcus Oliveira Andrade, Alfredo Mauricio Batista de Paula, André Luiz Sena Guimarães & Sérgio Henrique Sousa Santos

  2. Institute of Agricultural Sciences, Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Avenida Universitária, 1.000-Universitário, Montes Claros, MG, 39404-547, Brazil

    Junio Cota, Diego Vicente da Costa & Sérgio Henrique Sousa Santos

  3. Texas Tech University, Lubbock, TX, USA

    John David Feltenberger

  4. Department of Dentistry, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, MG, Brazil

    Alfredo Mauricio Batista de Paula & André Luiz Sena Guimarães

Authors
  1. Karla Nayara de Oliveira Santana
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  2. Deborah Farias Lelis
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  3. Keila Lopes Mendes
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  6. João Marcus Oliveira Andrade
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  9. Diego Vicente da Costa
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  10. Alfredo Mauricio Batista de Paula
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  12. Sérgio Henrique Sousa Santos
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Corresponding author

Correspondence to Sérgio Henrique Sousa Santos.

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de Oliveira Santana, K.N., Lelis, D.F., Mendes, K.L. et al. Metformin Reduces Lipogenesis Markers in Obese Mice Fed a Low-Carbohydrate and High-Fat Diet. Lipids 51, 1375–1384 (2016). https://doi.org/10.1007/s11745-016-4209-y

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  • DOI: https://doi.org/10.1007/s11745-016-4209-y

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