scholarly journals Paternal High-Protein Diet Programs Offspring Insulin Sensitivity in a Sex-Specific Manner

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 751
Author(s):  
Pengfei Gong ◽  
Danielle Bailbé ◽  
Lola Bianchi ◽  
Gaëlle Pommier ◽  
Junjun Liu ◽  
...  

The impact of maternal nutrition on offspring is well documented. However, the implication of pre-conceptional paternal nutrition on the metabolic health of the progeny remains underexplored. Here, we investigated the impact of paternal high-protein diet (HPD, 43.2% protein) consumption on the endocrine pancreas and the metabolic phenotype of offspring. Male Wistar rats were given HPD or standard diet (SD, 18.9% protein) for two months. The progenies (F1) were studied at fetal stage and in adulthood. Body weight, glycemia, glucose tolerance (GT), glucose-induced insulin secretion in vivo (GIIS) and whole-body insulin sensitivity were assessed in male and female F1 offspring. Insulin sensitivity, GT and GIIS were similar between F1 females from HPD (HPD/F1) and SD fathers (SD/F1). Conversely, male HPD/F1 exhibited increased insulin sensitivity (p < 0.05) and decreased GIIS (p < 0.05) compared to male SD/F1. The improvement of insulin sensitivity in HPD/F1 was sustained even after 2 months of high-fat feeding. In male HPD/F1, the β cell mass was preserved and the β cell plasticity, following metabolic challenge, was enhanced compared to SD/F1. In conclusion, we provide the first evidence of a sex-specific impact of paternal HPD on the insulin sensitivity and GIIS of their descendants, demonstrating that changes in paternal nutrition alter the metabolic status of their progeny in adulthood.

2019 ◽  
Vol 20 (7) ◽  
pp. 1547 ◽  
Author(s):  
Ewa Żebrowska ◽  
Mateusz Maciejczyk ◽  
Małgorzata Żendzian-Piotrowska ◽  
Anna Zalewska ◽  
Adrian Chabowski

This is the first study to analyze the impact of high protein diet (HPD) on antioxidant defense, redox status, as well as oxidative damage on both a local and systemic level. Male Wistar rats were divided into two equal groups (n = 9): HPD (44% protein) and standard diet (CON; 24.2% protein). After eight weeks, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase-1 (SOD-1), reduced glutathione (GSH), uric acid (UA), total antioxidant (TAC)/oxidant status (TOS) as well as advanced glycation end products (AGE), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were analyzed in the serum/plasma, cerebral cortex, and hypothalamus of HPD and CON rats. HPD resulted in higher UA concentration and activity of GPx and CAT in the hypothalamus, whereas in the cerebral cortex these parameters remained unchanged. A significantly lower GSH content was demonstrated in the plasma and hypothalamus of HPD rats when compared to CON rats. Both brain structures expressed higher content of 4-HNE and MDA, whereas AGE was increased only in the hypothalamus of HPD animals. Despite the enhancement in antioxidant defense in the hypothalamus, this mechanism does not protect the hypothalamus from oxidative damage in rats. Hypothalamus is more susceptible to oxidative stress caused by HPD.


1997 ◽  
pp. 701-708 ◽  
Author(s):  
A Blackburn ◽  
RA Dressendorfer ◽  
WF Blum ◽  
M Erhard ◽  
G Brem ◽  
...  

To study interactions between insulin-like growth factor-II (IGF-II) and growth hormone (GH) in vivo, we crossed hemizygous transgenic mice carrying phosphoenolpyruvate carboxykinase (PEPCK)-IGF-II fusion genes with hemizygous PEPCK-bovine GH (bGH) transgenic mice. Offspring harbouring both transgenes (IB), the IGF-II transgene (I) or the bGH transgene (B), and non-transgenic littermates (C) were obtained. Blood samples were taken before (end of week 12) and after (end of week 14) the mice had received a diet high in protein and low in carbohydrates to stimulate PEPCK promoter-controlled transgene expression. Mean serum GH concentrations of both B and IB mice corresponded to 900 ng/ml and increased more than twofold (P < 0.001) after 1 week of the high-protein diet. GH concentrations in controls and I mice were less than 20 ng/ml. Serum IGF-II concentrations in I and IB mice were three-to fourfold higher than those in C and B mice. Whereas IGF-II concentrations were not changed by the high-protein diet in the last two groups, serum IGF-II increased significantly in I (P < 0.001) and IB mice (P < 0.05). This increase was significantly (P < 0.05) less pronounced in IB than in C and I mice. Circulating IGF-I concentrations were about twofold (P < 0.001) higher in B and IB than in C and I mice, and showed a tendency to be lower in I than in C and in IB than in B mice when animals were maintained on the standard diet. The high-protein diet did not change circulating IGF-I concentrations in controls and B mice, but resulted in a significant reduction of serum IGF-I concentrations in I (P < 0.05) and IB mice (P < 0.001). Consequently, after PEPCK-IGF-II transgene expression was stimulated, serum IGF-I concentrations were significantly (P < 0.05) lower in I than in C and in IB than in B mice. Serum IGF-binding protein (IGFBP)-2 concentrations were significantly (P < 0.05) higher in I mice than in all other groups when mice were maintained on the standard diet, with a tendency to reduced IGFBP-2 concentrations in B mice. After the high-protein diet, serum IGFBP-2 concentrations did not change in C and I mice, but increased by two- to threefold in B and IB mice (P < 0.001). Serum IGFBP-3 concentrations tended to be greater in B and IB than in C and I mice, but these differences were mostly not significant. IGFBP-4 concentrations were significantly (P < 0.001) increased by GH overproduction in B and IB mice. Our data suggest that the reduction in circulating IGF-I concentrations by increased IGF-II is most probably due to the limited serum IGF binding capacity and the short half-life of free IGFs, rather than to a reduction in GH-dependent IGF-I production. Effects of GH overproduction on serum IGFBP-2 concentrations depend on dietary factors and may be both inhibitory and stimulatory.


1974 ◽  
Vol 142 (2) ◽  
pp. 359-364 ◽  
Author(s):  
J. D. McGivan ◽  
Norah M. Bradford ◽  
J. B. Chappell

1. Citrulline synthesis was measured in mitochondria from rats fed on a standard diet, a high-protein diet, or on glucose. 2. With NH4Cl as the nitrogen source the rate of citrulline synthesis was higher in mitochondria from rats fed on a high-protein diet than in those from rats fed on a standard diet. When rats were fed solely on glucose the rate of synthesis of citrulline from NH4Cl was very low. 3. With glutamate as the nitrogen source the relative rates of citrulline synthesis were much lower than when NH4Cl was present, but similar adaptive changes occurred. 4. The activity of the mitochondrial glutamate-transporting system increased two to three times on feeding rats on a high-protein diet, but the Km for glutamate was unchanged. 5. Adaptive changes in certain intramitochondrial enzymes were also measured. 6. The results were interpreted to indicate that when an excess of substrate was present, citrulline synthesis from NH4Cl was rate-limited by the intramitochondrial concentration of N-acetyl-glutamate, but citrulline synthesis from glutamate was rate-limited primarily by the activity of the glutamate-transporting system.


2018 ◽  
Vol 3 (4) ◽  
pp. 62
Author(s):  
Jose Antonio ◽  
Anya Ellerbroek ◽  
Cassandra Carson

The effects of long-term high-protein consumption (i.e., >2.2 g/kg/day) are unclear as it relates to bone mineral content. Thus, the primary endpoint of this investigation was to determine if consuming a high-protein diet for one year affected various parameters of body composition in exercise-trained women. This investigation is a follow-up to a prior 6-month study. Subjects were instructed to consume a high-protein diet (>2.2 g/kg/day) for one year. Body composition was assessed via dual-energy X-ray absorptiometry (DXA). Subjects were instructed to keep a food diary (i.e., log their food ~three days per week for a year) via the mobile app MyFitnessPal®. Furthermore, a subset of subjects had their blood analyzed (i.e., basic metabolic panel). Subjects consumed a high-protein diet for one year (mean ± SD: 2.3 ± 1.1 grams per kilogram body weight daily [g/kg/day]). There were no significant changes for any measure of body composition over the course of the year (i.e., body weight, fat mass, lean body mass, percent fat, whole body bone mineral content, whole body T-score, whole body bone mineral density, lumbar bone mineral content, lumbar bone mineral density and lumbar T-score). In addition, we found no adverse effects on kidney function. Based on this 1-year within-subjects investigation, it is evident that a diet high in protein has no adverse effects on bone mineral density or kidney function.


2008 ◽  
Vol 294 (1) ◽  
pp. E168-E175 ◽  
Author(s):  
Jamileh Movassat ◽  
Danièle Bailbé ◽  
Cécile Lubrano-Berthelier ◽  
Françoise Picarel-Blanchot ◽  
Eric Bertin ◽  
...  

The adult Goto-Kakizaki (GK) rat is characterized by impaired glucose-induced insulin secretion in vivo and in vitro, decreased β-cell mass, decreased insulin sensitivity in the liver, and moderate insulin resistance in muscles and adipose tissue. GK rats do not exhibit basal hyperglycemia during the first 3 wk after birth and therefore could be considered prediabetic during this period. Our aim was to identify the initial pathophysiological changes occurring during the prediabetes period in this model of type 2 diabetes (T2DM). To address this, we investigated β-cell function, insulin sensitivity, and body composition in normoglycemic prediabetic GK rats. Our results revealed that the in vivo secretory response of GK β-cells to glucose is markedly reduced and the whole body insulin sensitivity is increased in the prediabetic GK rats in vivo. Moreover, the body composition of suckling GK rats is altered compared with age-matched Wistar rats, with an increase of the number of adipocytes before weaning despite a decreased body weight and lean mass in the GK rats. None of these changes appeared to be due to the postnatal nutritional environment of GK pups as demonstrated by cross-fostering GK pups with nondiabetic Wistar dams. In conclusion, in the GK model of T2DM, β-cell dysfunction associated with increased insulin sensitivity and the alteration of body composition are proximal events that might contribute to the establishment of overt diabetes in adult GK rats.


1987 ◽  
Vol 253 (2) ◽  
pp. F318-F327
Author(s):  
A. Remuzzi ◽  
C. Battaglia ◽  
L. Rossi ◽  
C. Zoja ◽  
G. Remuzzi

Glomerular size-selective properties in animals made nephrotic by adriamycin (ADR) injection and fed standard (20% protein) or high-protein (35% protein) diets were investigated using dextran fractional clearances. To interpret filtration and dextran-sieving data, a theoretical approach previously developed for analysis of experimental data in healthy and nephrotic humans was used. Four types of hypothetical pore-radius distributions were compared in order to establish the best tool for describing membrane pore structure in normal and nephrotic rats. This analysis revealed that a spread distribution of pores, the lognormal probability distribution, is the most adequate in representing membrane intrinsic characteristics. ADR animals on standard diet developed massive proteinuria and a lower glomerular filtration rate (GFR) than control animals. High-protein feeding in ADR rats induced a further increase in urinary protein excretion and in GFR. Dextran fractional clearance was more elevated for larger dextran fractions (greater than 46 A) in ADR animals on the standard diet than in control rats. No differences were observed in dextran-sieving curves between ADR rats on the standard and high-protein diet. Theoretical analysis of filtration and fractional clearance data revealed comparable changes in the intrinsic parameters of glomerular size selectivity in the two groups of nephrotic animals. These observations indicate that increased traffic of plasma proteins through the glomerular capillary wall does not imply, in our experimental condition, a further loss of glomerular size-selective properties. The greater urinary protein excretion of ADR animals on high-protein diet than ADR animals on a standard diet cannot be explained by further impairment of glomerular size selectivity but more likely reflects hemodynamic changes.


2004 ◽  
Vol 16 (2) ◽  
pp. 190 ◽  
Author(s):  
D.K. Gardner ◽  
K.S. Stilley ◽  
M. Lane

Ammonium is known to adversely affect the development of mouse embryos in culture. Specifically, ammonium has been found to impair inner cell (ICM) mass formation, increase apoptosis, retard fetal development following embryo transfer and induce exencephaly. Significantly, high protein diets in cattle lead to reduced fecundity. This has been linked to elevated urea levels within fluid of the female tract. In this study we have determined the effects of a high protein diet for mice on the levels of ammonium within the female tract and the effects of such a diet on the development and viability of blastocysts developed in vivo. Outbred mice (CF1) were fed a diet of either 25% (high protein) or 14% (control) protein for 4 weeks. Females were superovulated and mated to males of the same strain. In 24 mice, oviduct fluid was collected at 22h post hCG. Ammonium in the oviduct fluid was then quantitated fluorometrically. From other animals, blastocysts were flushed 92h post hCG and analyzed. Blastocyst differentiation and apoptotic indices were determined. Values are mean±SEM. Data were analysed using Student’s t-test. The levels of ammonium in the oviduct were significantly higher (P&lt;0.01) in females fed the high protein diet (356±43μM) compared to the control (68±13μM) (n=12 in each group). Blastocysts (n=139) from females fed the high protein diet had significantly lower total (43.4±1.1; P&lt;0.05) and ICM cell numbers (12.7±0.4; P&lt;0.01), compared to the control group (46.8±0.9 and 15.4±0.4 respectively; n=124). Furthermore, blastocysts from animals fed a high protein diet had a significantly higher apoptotic index (8.7±1.4; P&lt;0.01) compared to the control group (2.0±0.5). These data show that consumption of a high protein diet results in the excess accumulation of ammonium in the fluid of the female reproductive tract of mice. These high levels of ammonium subsequently impair the formation of the fetal progenitor cells and increase cell death at the blastocyst stage. These data from in vivo-developed mouse blastocysts are similar to those for blastocysts developed in culture in the presence of 300μM ammonium. Therefore, it is not advisable to maintain mice on a high protein diet. These data have significant implications for animal breeding, and for patients attempting IVF treatment.


2019 ◽  
Vol 317 (6) ◽  
pp. E1015-E1021 ◽  
Author(s):  
Tristan Chalvon-Demersay ◽  
Joanna Moro ◽  
Patrick C. Even ◽  
Catherine Chaumontet ◽  
Daniel Tomé ◽  
...  

General control nonderepressible 2 (GCN2) is a kinase that detects amino acid deficiency and is involved in the control of protein synthesis and energy metabolism. However, the role of hepatic GCN2 in the metabolic adaptations in response to the modulation of dietary protein has been seldom studied. Wild-type (WT) and liver GCN2-deficient (KO) mice were fed either a normo-protein diet, a low-protein diet, or a high-protein diet for 3 wk. During this period, body weight, food intake, and metabolic parameters were followed. In mice fed normo- and high-protein diets, GCN2 pathway in the liver is not activated in WT mice, leading to a similar metabolic profile with the one of KO mice. On the contrary, a low-protein diet activates GCN2 in WT mice, inducing FGF21 secretion. In turn, FGF21 maintains a high level of lipid oxidation, leading to a different postprandial oxidation profile compared with KO mice. Hepatic GCN2 controls FGF21 secretion under a low-protein diet and modulates a whole body postprandial oxidation profile.


Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 514 ◽  
Author(s):  
Sandra Vidal-Lletjós ◽  
Mireille Andriamihaja ◽  
Anne Blais ◽  
Marta Grauso ◽  
Patricia Lepage ◽  
...  

Mucosal healing after an inflammatory flare is associated with lasting clinical remission. The aim of the present work was to evaluate the impact of the amount of dietary protein on epithelial repair after an acute inflammatory episode. C57BL/6 DSS-treated mice received isocaloric diets with different levels of dietary protein: 14% (P14), 30% (P30) and 53% (P53) for 3 (day 10), 6 (day 13) and 21 (day 28) days after the time of colitis maximal intensity. While the P53 diet worsened the DSS- induced inflammation both in intensity and duration, the P30 diet, when compared to the P14 diet, showed a beneficial effect during the epithelial repair process by accelerating inflammation resolution, reducing colonic permeability and increasing epithelial repair together with epithelial hyperproliferation. Dietary protein intake also impacted mucosa-adherent microbiota composition after inflammation since P30 fed mice showed increased colonization of butyrate-producing genera throughout the resolution phase. This study revealed that in our colitis model, the amount of protein in the diet modulated mucosal healing, with beneficial effects of a moderately high-protein diet, while very high-protein diet displayed deleterious effects on this process.


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