- Marleen A. Baak van (1)
- Janneke Dopheide (1)
- Rubén Díaz-Rúa (1)
- Karianna F.M. Teunissen-Beekman (1)
- Marianne Geleijnse (1)
- Elizabeth J. Brink (1)
- Stephan J.L. Bakker (1)
- Jaap Keijer (1)
- Evert M. Schothorst van (1)
- Paula Oliver (1)
- Andreu Palou (1)
- Peter W. Leeuw de (1)
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 - \ 2017
Journal of Nutritional Biochemistry 46 (2017). - ISSN 0955-2863 - p. 39 - 48.
Acid load - Hyperproteic diet - Liver disease - Liver steatosis - Microarray analysis
Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acid–base maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acid–base equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences.
Effect of increased protein intake on renal acid load and renal hemodynamic responses
Teunissen-Beekman, Karianna F.M. ; Dopheide, Janneke ; Geleijnse, Marianne ; Bakker, Stephan J.L. ; Brink, Elizabeth J. ; Leeuw, Peter W. de; Baak, Marleen A. van - \ 2016
Physiological Reports 4 (2016)5. - ISSN 2051-817X - 10 p.
Acid load - Carbohydrate - Glomerular filtration rate - Kidney - Protein
Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high-protein diets reduce renal function. Effects of acute and 4-week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy-nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty-four-hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein- or maltodextrin-load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P ≤ 0.001). Postprandial filtration fraction decreased further after the protein-supplemented breakfast than after the maltodextrin-supplemented breakfast after 4 weeks of supplementation (P ≤ 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin-converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function.