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A Low-Protein, High-Carbohydrate Diet Increases Fatty Acid Uptake and Reduces Norepinephrine-Induced Lipolysis in Rat Retroperitoneal White Adipose Tissue

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Lipids

Abstract

A low-protein, high-carbohydrate (LPHC) diet for 15 days increased the lipid content in the carcass and adipose tissues of rats. The aim of this work was to investigate the mechanisms of this lipid increase in the retroperitoneal white adipose tissue (RWAT) of these animals. The LPHC diet induced an approximately two- and tenfold increase in serum corticosterone and TNF-α, respectively. The rate of de novo fatty acid (FA) synthesis in vivo was reduced (50%) in LPHC rats, and the lipoprotein lipase activity increased (100%). In addition, glycerokinase activity increased (60%), and the phosphoenolpyruvate carboxykinase content decreased (27%). Basal [U-14C]-glucose incorporation into glycerol-triacylglycerol did not differ between the groups; however, in the presence of insulin, [U-14C]-glucose incorporation increased by 124% in adipocytes from only control rats. The reductions in IRS1 and AKT content as well as AKT phosphorylation in the RWAT from LPHC rats and the absence of an insulin response suggest that these adipocytes have reduced insulin sensitivity. The increase in NE turnover by 45% and the lack of a lipolytic response to NE in adipocytes from LPHC rats imply catecholamine resistance. The data reveal that the increase in fat storage in the RWAT of LPHC rats results from an increase in FA uptake from circulating lipoproteins and glycerol phosphorylation, which is accompanied by an impaired lipolysis that is activated by NE.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

AKT:

Serine/threonine protein kinase

ATGL:

Adipose triglyceride lípase

cAMP:

Cyclic adenosine monophosphate

EAT:

Epididymal adipose tissue

EtOH:

Ethyl alcohol

FA:

Fatty acids

FFA:

Free fatty acid

G3P:

Glycerol-3-phosphate

GLUT-4:

Glucose transporter type 4

GyK:

Glycerokinase

HPA:

Hypothalamic-pituitary-adrenal axis

HSL:

Hormone-sensitive lipase

IR:

Insulin receptor

IRS-1:

Insulin receptor substrate 1

LPHC:

Low-protein, high-carbohydrate diet

LPL:

Lipoprotein lipase

NE:

Norepinephrine

PDE3B:

Phosphodiesterase 3B

PEPCK:

Phosphoenolpyruvate carboxykinase

PI3K:

Phosphotidylinositol 3-kinase

PKA:

Protein kinase A

PPARγ:

Peroxisome proliferator-activated receptors γ

RWAT:

Retroperitoneal white adipose tissue

SE:

Standard error

T3:

Triiodothyronine

T4:

Thyroxine

TAG:

Triacylglycerol

TNF-α:

Tumor necrosis factor-α

WAT:

White adipose tissue

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Acknowledgments

We thank Air Francisco Costa, Marlene Mariano and Celso Roberto Afonso for their technical assistance. We also thank Renato Hélios Migliorini in memoriam for being an exemplary scientist and professor. This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de Mato Grosso (FAPEMAT) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Department of Chemistry, Federal University of Mato Grosso, Cuiabá, MT, Brazil

    Maísa P. dos Santos, Suélem A. de França, José Tiago F. dos Santos, Samyra L. Buzelle & Nair H. Kawashita

  2. Department of Basic Sciences in Health, Federal University of Mato Grosso, Cuiabá, MT, Brazil

    Gisele L. Bertolini & Valéria E. Chaves

  3. Department of Physiology, University of São Paulo, Ribeirão Preto, SP, Brazil

    Maria Antonieta R. Garófalo

  4. Department of Biochemistry, Immunology, University of São Paulo, Ribeirão Preto, SP, Brazil

    Isis C. do Kettelhut & Danúbia Frasson

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  1. Maísa P. dos Santos
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  2. Suélem A. de França
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  3. José Tiago F. dos Santos
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Correspondence to Nair H. Kawashita.

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dos Santos, M.P., de França, S.A., dos Santos, J.T.F. et al. A Low-Protein, High-Carbohydrate Diet Increases Fatty Acid Uptake and Reduces Norepinephrine-Induced Lipolysis in Rat Retroperitoneal White Adipose Tissue. Lipids 47, 279–289 (2012). https://doi.org/10.1007/s11745-011-3648-8

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