Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats

Díaz‐Rúa, Rubén; Keijer, Jaap; Palou, Andreu; Schothorst, Evert M. van; Oliver, Paula

doi:10.1016/j.jnutbio.2017.04.008

Cited by 37 publications

(37 citation statements)

References 53 publications

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“…methionine and cysteine found in animal protein) in the liver can directly cause liver injury (59). Lastly, an experimental rat study found that a high protein diet upregulated mRNA expression of genes encoding proteins involved in amino acid uptake and enhanced lipid synthesis (60). In this study, hepatic mRNA and protein levels of heat shock protein 90, a marker of liver injury, were markedly increased in these rats fed a high-protein diet.…”

Section: Discussionmentioning

confidence: 52%

Diet-Dependent Acid Load—The Missing Link Between an Animal Protein–Rich Diet and Nonalcoholic Fatty Liver Disease?

Alferink

Jong

Erler

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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Objective Our group recently showed that animal protein was independently associated with nonalcoholic fatty liver disease (NAFLD). We hypothesize that this may be explained by a high diet-dependent acid load [dietary acid load (DAL)]. Methods This cross-sectional study is embedded in a prospective population-based cohort. We estimated DAL proxies via food-frequency questionnaires using potential renal acid load (PRAL; using dietary protein, phosphorus, potassium, calcium, and magnesium intake), net endogenous acid production (NEAP; using protein and potassium intake), and the animal protein–to–potassium ratio (A:P). We defined NAFLD using ultrasound after excluding secondary steatogenic causes. We used logistic regression models—adjusted for sociodemographic, lifestyle, and metabolic traits—on categorized [quartile (Q)1 to 4] and continuous DAL proxies (allowing for nonlinearity) and NAFLD. Results We included 3882 participants, of which 1337 had NAFLD. All DAL proxies were higher, meaning more acidic, in individuals with NAFLD (PRAL, −2.9 vs −5.5 mEq/d; NEAP, 37.0 vs 35.1 mEq/d; and A:P, 13.3 vs 12.4; all P < 0.001). The highest Q of DAL proxies was associated with NAFLD independent of sociodemographic and lifestyle confounders, but significance dissipated after correction for metabolic confounders and multiple testing. However, the P value for nonlinearity was significant in all DAL proxies (P < 0.001). Natural cubic splines performed better with than without DAL proxies in the fully adjusted model (all P ≤ 0.038). The highest probability of NAFLD was found for an acidic diet. Conclusions This study showed an independent nonlinear association between an acidic diet and NAFLD. Further studies with acid-base biomarkers are needed, but our findings might provide a mechanistic explanation for the harmful association between an animal protein–rich diet and NAFLD.

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Section: Discussionmentioning

confidence: 52%

Diet-Dependent Acid Load—The Missing Link Between an Animal Protein–Rich Diet and Nonalcoholic Fatty Liver Disease?

Alferink

Jong

Erler

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…But this was expected because the levels of proteins used are only considered as to supply a source of bioactive compounds, then this trail is not considered as a high protein rich diet supplementation, which is associated with body weight loss [29]. However because the amount of protein administered is not considered as a HP-diet, it also does not causes the problems of health deterioration as reported recently [30]. But most important, it has been described that the type of protein could have different effects on body weight [31].…”

Section: Discussionmentioning

confidence: 99%

Amaranth Protein Improves Lipid Profile and Insulin Resistance in a Diet-induced Obese Mice Model

Escobedo-Moratilla¹,

Velarde‐Salcedo²,

Magaña-Hernández³

et al. 2017

JFNR

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Amaranth has been claimed as functional food, but its function on obesity-related disorder is not fully known. The aim of this study was to analyse the effect of amaranth protein intake on blood lipids profile and insulin resistance in diet-induced obese mice. The effect of soybean protein was also analysed for comparative purposes. C57BL-6 mice were fed for eight weeks with regular or high fat diet. Amaranth or soybean protein isolates (10 mg/kg) were supplied via oral administration. Changes in body weight, adipose tissue, total cholesterol, triglycerides, insulin, a glucose tolerance test, as well as the expression of lipid metabolism-related genes were measured. Our results have shown that amaranth protein induces a decrease in plasma insulin in mice fed with a regular diet, whereas a decrease in triglycerides was observed in mice fed with high fat diet. Furthermore, down-regulation of Tnf-α and Res, suggested the inhibition of inflammation state. The present study demonstrates that amaranth protein, but not soybean protein, improves the obese mice health, and the hormonal modulation (Lep, Fasn, Lpl) could lead to new mechanism of action by which amaranth consumption exerts its beneficial health effect.

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“…Excess protein in the diet (including whey proteins) can adversely affect the activity of the organs participating in its metabolism [ 6 ]. One of such organs is the liver.…”

Section: Introductionmentioning

confidence: 99%

“…It has been demonstrated that high-protein diet may result in a positive nitrogen balance, which causes increased production of urea and ammonia in the urea cycle [ 7 ]. This situation may lead to a significant overload of the liver [ 6 , 8 ]. One of the markers used to assess liver function are lysosomal exoglycosidases: N-acetyl-β- D -hexosaminidase (HEX, EC 3.2.1.52), β-glucuronidase (GLU, EC 3.2.1.31), β-galactosidase (GAL, EC 3.2.1.23), α-mannosidase (MAN, EC 3.2.1.24) and α-fucosidase (FUC, EC 3.2.1.51) [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Lipids are the first to suffer oxidative damage, as they are the most susceptible to oxygen free radicals [ 16 , 17 ]. Although increased production of ROS under the influence of rich protein diet has been demonstrated in numerous organs (brain [ 18 ], pancreas [ 19 ], salivary glands [ 20 ] and liver [ 6 ]), the effect of whey on liver oxidative damage is still unknown. Whey reveals documented antioxidant properties [ 21 ] but it has not been established yet whether whey-induced boost in GSH synthesis can prevent oxidative stress in the conditions of increased protein supply.…”

Section: Introductionmentioning

confidence: 99%

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Whey Protein Concentrate WPC-80 Intensifies Glycoconjugate Catabolism and Induces Oxidative Stress in the Liver of Rats

et al. 2018

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The aim of this study was to evaluate the effect of whey protein concentrate (WPC-80) on glycoconjugate catabolism, selected markers of oxidative stress and liver inflammation. The experiment was conducted on male Wistar rats (n = 63). The animals from the study group were administered WPC-80 at a dose of 0.3 or 0.5 g/kg body weight for 7, 14 or 21 days, while rats from the control group received only 0.9% NaCl. In liver homogenates, we assayed the activity of N-acetyl-β-D-hexosaminidase (HEX), β-glucuronidase (GLU), β-galactosidase (GAL), α-mannosidase (MAN), α-fucosidase (FUC), as well as the level of reduced glutathione (GSH), malondialdehyde (MDA), interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1). A significantly higher activity of HEX, GLU, MAN and FUC were found in the livers of rats receiving WPC-80 compared to controls. Serum ALT and AST were significantly higher in the animals supplemented with WPC-80 at a dose of 0.5 g/kg body weight for 21 days. In the same group of animals, enhanced level of GSH, MDA, IL-1β and TGF-β1 were also observed. WPC-80 is responsible for intensive remodelling of liver tissue and induction of oxidative stress especially at a dose of 0.5 g/kg body weight.

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Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats

Cited by 37 publications

References 53 publications

Diet-Dependent Acid Load—The Missing Link Between an Animal Protein–Rich Diet and Nonalcoholic Fatty Liver Disease?

Diet-Dependent Acid Load—The Missing Link Between an Animal Protein–Rich Diet and Nonalcoholic Fatty Liver Disease?

Amaranth Protein Improves Lipid Profile and Insulin Resistance in a Diet-induced Obese Mice Model

Whey Protein Concentrate WPC-80 Intensifies Glycoconjugate Catabolism and Induces Oxidative Stress in the Liver of Rats

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