A High-Protein Diet Promotes Atrial Arrhythmogenesis via Absent-in-Melanoma 2 Inflammasome.

High-protein diets (HPDs) offer health benefits, such as weight management and improved metabolic profiles. The effects of HPD on cardiac arrhythmogenesis remain unclear. Atrial fibrillation (AF), the most common arrhythmia, is associated with inflammasome activation. The role of the Absent-in-Melanoma 2 (AIM2) inflammasome in AF pathogenesis remains unexplored. In this study, we discovered that HPD increased susceptibility to AF. To demonstrate the involvement of AIM2 signaling in the pathogenesis of HPD-induced AF, wildtype (WT) and Aim2-/- mice were fed normal-chow (NC) and HPD, respectively. Four weeks later, inflammasome activity was upregulated in the atria of WT-HPD mice, but not in the Aim2-/--HPD mice. The increased AF vulnerability in WT-HPD mice was associated with abnormal sarcoplasmic reticulum (SR) Ca2+-release events in atrial myocytes. HPD increased the cytoplasmic double-strand (ds) DNA level, causing AIM2 activation. Genetic inhibition of AIM2 in Aim2-/- mice reduced susceptibility to AF, cytoplasmic dsDNA level, mitochondrial ROS production, and abnormal SR Ca2+-release in atrial myocytes. These data suggest that HPD creates a substrate conducive to AF development by activating the AIM2-inflammasome, which is associated with mitochondrial oxidative stress along with proarrhythmic SR Ca2+-release. Our data imply that targeting the AIM2 inflammasome might constitute a novel anti-AF strategy in certain patient subpopulations.

Effects of a High-Protein Diet on Kidney Injury under Conditions of Non-CKD or CKD in Mice.

Considering the prevalence of obesity and global aging, the consumption of a high-protein diet (HPD) may be advantageous. However, an HPD aggravates kidney dysfunction in patients with chronic kidney disease (CKD). Moreover, the effects of an HPD on kidney function in healthy individuals are controversial. In this study, we employed a remnant kidney mouse model as a CKD model and aimed to evaluate the effects of an HPD on kidney injury under conditions of non-CKD and CKD. Mice were divided into four groups: a sham surgery (sham) + normal diet (ND) group, a sham + HPD group, a 5/6 nephrectomy (Nx) + ND group and a 5/6 Nx + HPD group. Blood pressure, kidney function and kidney tissue injury were compared after 12 weeks of diet loading among the four groups. The 5/6 Nx groups displayed blood pressure elevation, kidney function decline, glomerular injury and tubular injury compared with the sham groups. Furthermore, an HPD exacerbated glomerular injury only in the 5/6 Nx group; however, an HPD did not cause kidney injury in the sham group. Clinical application of these results suggests that patients with CKD should follow a protein-restricted diet to prevent the exacerbation of kidney injury, while healthy individuals can maintain an HPD without worrying about the adverse effects.

L-Theanine Mitigates the Harmful Effects of Excess High-Protein Diet in Rats by Regulating Protein Metabolism.

SCOPE: l-Theanine (LTA) is a non-protein amino acid that contributes to the flavor of tea and can regulate protein metabolism of healthy organisms. However, it is unknown whether it regulates protein metabolism in individuals on high-protein diets (HPDs). METHODS AND RESULTS: Here, Sprague-Dawley rats are fed HPDs with different protein supply ratios and administered a diverse dose of LTA for 40 days. Results show that HPDs with an energy supply ratio from protein >40% impair the liver and kidneys, elevate serum ammonia and urea nitrogen, induce amino acid (AA) catabolism, and promote fatty acid (FA) synthesis via FA-binding protein 5 (Fabp5) and acetyl-CoA carboxylase 1 (ACC1). LTA intervention alleviates HPD-induced hepatic and renal injury and improves serum biochemical indices. It increases hepatic free AA content and inhibits FA synthesis by downregulating Fabp5 and ACC1. It promotes protein synthesis by acting on the mammalian target of rapamycin (mTOR) pathway, thereby alleviating HPD-induced metabolic disorders. CONCLUSIONS: This study demonstrates that LTA mitigates kidney and liver damage induced by long-term excess HPDs by regulating protein metabolism.

A Specific High-Protein Weight Loss Program Does Not Impair Renal Function in Patients Who Are Overweight/Obese.

Although high-protein diets appear to be the most efficient way to lose weight, concerns may arise about their innocuity on renal function. The objective of this study is to assess the impact of a weight loss program on renal function. A multicentric cohort-based study was performed using the RNPC© French national weight loss program. Patients with at least two creatinine measurements at the beginning of the program and at the end of the weight loss phase between 1 January 2016 and 1 July 2021 were included. Renal function was assessed by Modification of Diet in Renal Disease (MDRD) equation-based estimated glomerular filtration rate (eGFR). From 4394 patients with two creatinine measurements included, 1579 (35.9%) had normal eGFR (MDRD 90-120 mL/min/1.73 m2), 210 (4.8%) had hyperfiltration (MDRD > 120 mL/min/1.73 m2), 2383 (54.2%) had chronic kidney disease (CKD) grade 2 (MDRD 60-90 mL/min/1.73 m2), and 221 (5.0%) had CKD grade 3 (MDRD 30-60 mL/min/1.73 m2). Multivariable analyses showed no eGFR change for patients in initial CKD grade 2, normal eGFR and hyperfiltration, and a significant increase in CKD grade 3. The RNPC© program avoids renal function impairment during the two first phases, regardless of the initial eGFR.

Effect of different protein based feed on the growth of mahseer / Efeito de alimentação baseada em proteínas diferentes no crescimento de mahseer

For the proper growth of fish, it is necessary to feed the fish with a proper and balanced diet. A study was conducted to find out the effect of different protein-based diets on fingerlings of Tor putitora (mahseer). A feed with dietary protein levels of 35%, 40%, 45%, and 50% were prepared. The effect of different protein-based feed on weight gain, standard growth rate (SGR), food conversion ratio (FCR), percent weight gain, food conversion efficiency (FCE), and protein efficiency ratio (PER) was studied. An increase was observed in the growth rate with an increase in protein concentration up to 45%. The fingerlings fed a 45% protein diet shown the highest growth, followed by 50%, 40%, and 35%. The SGR value was greatest for 45% protein diet (8.56) followed by 50% and 40%, while the least values were observed for 35% protein feed (1.57). The same trend was observed for FCE. The highest PER values was observed in fishes fed 45% protein-based feed (0.65) followed by 50% (0.56), 40% (0.38) and35% (0.17). The food conversion ratio was lowest for 45% protein diet (3.41), while the greatest for 35% protein feed (16.85). It was concluded that a 45% protein-based diet was the best feed formulation for higher production of Tor putitora. However, research on the same percentage of protein diet is recommended for yearlings.

Para o bom crescimento dos peixes, é necessário alimentá-los com uma alimentação adequada e balanceada. Um estudo foi realizado para descobrir o efeito de diferentes dietas à base de proteínas em alevinos de Tor putitora (mahseer). Foi preparado um alimento com níveis de proteína dietética de 35%, 40%, 45% e 50%. O efeito de diferentes alimentos à base de proteína no ganho de peso, taxa de crescimento padrão (SGR), taxa de conversão alimentar (FCR), ganho de peso percentual, eficiência de conversão alimentar (FCE) e taxa de eficiência proteica (PER) foi estudado. Foi observado um aumento na taxa de crescimento com um aumento na concentração de proteína de até 45%. Os alevinos alimentados com dieta de 45% de proteína apresentaram o maior crescimento, seguidos de 50%, 40% e 35%. O valor de SGR foi maior para dieta com 45% de proteína (8,56), seguido de 50% e 40%, enquanto os menores valores foram observados para ração com 35% de proteína (1,57). A mesma tendência foi observada para FCE. Os maiores valores de PER foram observados em peixes alimentados com 45% de ração à base de proteína (0,65), seguido por 50% (0,56), 40% (0,38) e 35% (0,17). A taxa de conversão alimentar foi menor para a dieta com 45% de proteína (3,41), enquanto a maior para a dieta com 35% de proteína (16,85). Concluiu-se que a dieta à base de proteína de 45% foi a melhor formulação alimentar para maior produção de Tor putitora. No entanto, a pesquisa sobre a mesma porcentagem de dieta proteica é recomendada para animais de um ano.

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

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 ß cell mass was preserved and the ß 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.

Urinary Medium-Chained Acyl-Carnitines Sign High Caloric Intake whereas Short-Chained Acyl-Carnitines Sign High -Protein Diet within a High-Fat, Hypercaloric Diet in a Randomized Crossover Design Dietary Trial.

The western dietary pattern is known for its frequent meals rich in saturated fat and protein, resulting in a postprandial state for a large part of the day. Therefore, our aim was to investigate the postprandial glucose and lipid metabolism in response to high (HP) or normal (NP) protein, high-fat hypercaloric diet and to identify early biomarkers of protein intake and hepatic lipid accumulation. In a crossover design, 17 healthy subjects were randomly assigned to consume a HP or NP hypercaloric diet for two weeks. In parallel, a control group (CD; n = 10) consumed a weight-maintaining control diet. Biomarkers of postprandial lipid and glucose metabolism were measured in 24 h urine and in plasma before and following a meal challenge. The metabolic profile of urine but not plasma, showed increased excretion of 13C, carnitine and short chain acyl-carnitines after adaptation to the HP diet. Urinary excretion of decatrienoylcarnitine and octenoylcarnitine increased after adaptation to the NP diet. Our results suggest that the higher excretion of short-chain urinary acyl-carnitines could facilitate the elimination of excess fat of the HP diet and thereby reduce hepatic fat accumulation previously reported, whereas the higher excretion medium-chains acyl-carnitine could be early biomarkers of hepatic lipid accumulation.

Old Question Revisited: Are High-Protein Diets Safe in Pregnancy?

BACKGROUND: A previous randomized dietary intervention in pregnant women from the 1970s, the Harlem Trial, reported retarded fetal growth and excesses of very early preterm births and neonatal deaths among those receiving high-protein supplementation. Due to ethical challenges, these findings have not been addressed in intervention settings. Exploring these findings in an observational setting requires large statistical power due to the low prevalence of these outcomes. The aim of this study was to investigate if the findings on high protein intake could be replicated in an observational setting by combining data from two large birth cohorts. METHODS: Individual participant data on singleton pregnancies from the Danish National Birth Cohort (DNBC) (n = 60,141) and the Norwegian Mother, Father and Child Cohort Study (MoBa) (n = 66,302) were merged after a thorough harmonization process. Diet was recorded in mid-pregnancy and information on birth outcomes was extracted from national birth registries. RESULTS: The prevalence of preterm delivery, low birth weight and fetal and neonatal deaths was 4.77%, 2.93%, 0.28% and 0.17%, respectively. Mean protein intake (standard deviation) was 89 g/day (23). Overall high protein intake (>100 g/day) was neither associated with low birth weight nor fetal or neonatal death. Mean birth weight was essentially unchanged at high protein intakes. A modest increased risk of preterm delivery [odds ratio (OR): 1.10 (95% confidence interval (CI): 1.01, 1.19)] was observed for high (>100 g/day) compared to moderate protein intake (80-90 g/day). This estimate was driven by late preterm deliveries (weeks 34 to <37) and greater risk was not observed at more extreme intakes. Very low (<60 g/day) compared to moderate protein intake was associated with higher risk of having low-birth weight infants [OR: 1.59 (95%CI: 1.25, 2.03)]. CONCLUSIONS: High protein intake was weakly associated with preterm delivery. Contrary to the results from the Harlem Trial, no indications of deleterious effects on fetal growth or perinatal mortality were observed.

Long Term High Protein Diet Feeding Alters the Microbiome and Increases Intestinal Permeability, Systemic Inflammation and Kidney Injury in Mice.

SCOPE: This study evaluates the effects of a chronic high protein diet (HPD) on kidney injury, intestinal permeability and gut microbiota perturbations in a mouse model. METHOD AND RESULTS: Mice are fed a diet containing either 20% or 52% energy from protein for 24 weeks; protein displaced an equivalent amount of wheat starch. The HPD does not alter glycemic control or body weight. The HPD induces kidney injury as evidenced by increase in albuminuria, urinary kidney injury molecule-1, blood urea nitrogen, urinary isoprostanes and renal cortical NF-κB p65 gene expression. HPD decreases intestinal occludin gene expression, increases plasma endotoxin and plasma monocyte chemoattractant protein-1, indicating intestinal leakiness and systemic inflammation. Cecal microbial analysis reveals that HPD feeding does not alter alpha diversity; however, it does alter beta diversity, indicating an altered microbial community structure with HPD feeding. Predicted metagenome pathway analysis demonstrates a reduction in branched-chain amino acid synthesis and an increase of the urea cycle with consumption of a HPD. CONCLUSION: These results demonstrate that long term HPD consumption in mice causes albuminuria, systemic inflammation, increase in gastrointestinal permeability and is associated with gut microbiome remodeling with an increase in the urea cycle pathway, which may contribute to renal injury.

Does high dietary protein intake contribute to the increased risk of developing prediabetes and type 2 diabetes?

Insulin resistance is a complex metabolic disorder implicated in the development of many chronic diseases. While it is generally accepted that body mass loss should be the primary approach for the management of insulin resistance-related disorders in overweight and obese individuals, there is no consensus among researchers regarding optimal protein intake during dietary restriction. Recently, it has been suggested that increased plasma branched-chain amino acids concentrations are associated with the development of insulin resistance and type 2 diabetes. The exact mechanism by which excessive amino acid availability may contribute to insulin resistance has not been fully investigated. However, it has been hypothesised that mammalian target of rapamycin (mTOR) complex 1 hyperactivation in the presence of amino acid overload contributes to reduced insulin-stimulated glucose uptake because of insulin receptor substrate (IRS) degradation and reduced Akt-AS160 activity. In addition, the long-term effects of high-protein diets on insulin sensitivity during both weight-stable and weight-loss conditions require more research. This review focusses on the effects of high-protein diets on insulin sensitivity and discusses the potential mechanisms by which dietary amino acids can affect insulin signalling. Novelty: Excess amino acids may over-activate mTOR, resulting in desensitisation of IRS-1 and reduced insulin-mediated glucose uptake.

Maternal high protein-diet programs impairment of offspring's bone mass through miR-24-1-5p mediated targeting of SMAD5 in osteoblasts.

Maternal nutrition is crucial for the offspring's skeleton development and the onset of osteoporosis later in life. While maternal low protein diet has been shown to regulate bone mass negatively, the effect of a high protein diet (HP) remains unexplored. Here, we found that C57BL/6 mice fed with HP delivered offspring with decreased skeletal mineralization at birth and reduced bone mass throughout their life due to a decline in their osteoblast maturation. A small RNA sequencing study revealed that miR-24-1-5p was highly upregulated in HP group osteoblasts. Target prediction and validation studies identified SMAD-5 as a direct target of miR-24-1-5p. Furthermore, mimic and inhibitor studies showed a negative correlation between miR-24-1-5p expression and osteoblast function. Moreover, ex vivo inhibition of miR-24-1-5p reversed the reduced maturation and SMAD-5 expression in the HP group osteoblasts. Together, we show that maternal HP diminishes the bone mass of the offspring through miR-24-1-5p.

Metabolomic analysis of organic acids, amino acids, and fatty acids in plasma of Hanwoo beef on a high-protein diet.

INTRODUCTION: Ketoacidosis of metabolic disease showed in beef cattle although body weight was increased by high-grain diets (HGDs). However, few studies have examined for health status related with metabolic disease of ketoacidosis following high-protein diet (HPD). OBJECTIVES: Metabolomic analysis was performed for the monitoring of health status associated with metabolic disease of ketoacidosis in the plasma of Hanwoo heifers following a HPD. METHODS: Hanwoo heifers of 24 months with 459 ± 42 kg weight were used under a 2 × 2 crossover design. The plasma was collected from control (n = 5) and HPD group (n = 5) on day 21 following diet adaptation for 20 days. Metabolic profiling analysis of organic acids (OAs), amino acids (AAs) and fatty acids (FAs) by gas chromatography-tandem mass spectrometry combined with star pattern analysis was performed in plasma. Levels of OAs, AAs and FAs were evaluated by Mann-Whitney test, PCA and PLS-DA. RESULTS: In HPD group, ketoacidosis as metabolic disease was monitored by elevated acetoacetic acid and 3-hydroxybutyric acid. In addition, the elevation of ketogenic AAs, reduction of medium chain FAs and OAs with energy metabolism in TCA cycle were monitored in HPD group. Star graphic pattern was characteristic and readily distinguished between control and HPD groups. In PLS-DA, two groups were separated with VIP score of top-ranked 10 FAs as important metabolites for discrimination. CONCLUSION: Elevation of ketone body including ketogenic AAs and reduced energy metabolism of FAs and OAs may useful for evaluation of health states associated with ketoacidosis from metabolic event by HPD in beef cattle.

Gut inflammation exacerbates hepatic injury in C57BL/6J mice via gut-vascular barrier dysfunction with high-fat-incorporated meat protein diets.

AIM: Meat and its derivatives provide nutrients essential for human health. However, meat consumption, along with excessive fat intake, has been associated with gut inflammation, intestinal barrier dysfunction and alterations in gut microbiota. Herein, we investigated whether and how these changes in the intestinal barrier system affect the gut liver axis and hepatic injury and eventually lead to the progression of liver syndrome such as NAFLD. METHODS: Mice were fed with high fat (60% kcal) or low fat (12% kcal) along with soybean (control), chicken and pork proteins (HFCH, HFP, LFCH, and LFP) for 12 weeks. The biomarkers for liver injury were investigated after meat protein intake along with the high fat. FINDINGS: Greater amount of fat vacuoles visible in the H&E staining increased the inflammatory cell infiltration and disorganized liver structures were observed in the HFP-fed mice. Oil Red O staining revealed that the HFP-fed and HFCH-fed mice showed more lipid droplets, confirming the increased hepatic lipid accumulation. Potential serum markers for NAFLD, ALT and AST were increased in the HF meat diet groups. Key genes responsible for hepatic inflammation and lipogenesis, such as MCP-1, IL1-ß and TNF-α were upregulated. HF meat protein diet-fed mice exhibited signs of compromised liver with increased levels of endotoxin in the liver and its binding protein in serum, upregulation of TLRs in the liver, and significant increase in TG, TC, LDL-C and HDL-C concentrations. SIGNIFICANCE: Intestinal inflammation and barrier dysfunction aggravate liver injury and fibrosis due to the intake of HF meat protein diets in mice, which may contribute to the progress of liver injury and associated complications. Gut inflammation may directly contribute to the development of NAFLD, especially of the gut vascular barricade dysfunction.

Dietary protein intake and obesity-associated cardiometabolic function.

PURPOSE OF REVIEW: High-protein intake is commonly recommended to help people manage body weight. However, high-protein intake could have adverse health consequences. Here we review the latest findings concerning the effect of high-protein intake on cardiometabolic health. RECENT FINDINGS: Calorie-reduced, high-protein, low-carbohydrate diets lower plasma glucose in people with type 2 diabetes (T2D). However, when carbohydrate intake is not markedly reduced, high-protein intake often does not alter plasma glucose and increases insulin and glucagon concentrations, which are risk factors for T2D and ischemic heart disease. High-protein intake does not alter plasma triglyceride and cholesterol concentrations but promotes atherogenesis in animal models. The effect of high-protein intake on liver fat remains unclear. In population studies, high-protein intake is associated with increased risk for T2D, nonalcoholic fatty liver disease, and possibly cardiovascular diseases. SUMMARY: The relationship between protein intake and cardiometabolic health is complex and influenced by concomitant changes in body weight and overall diet composition. Although a high-protein, low-carbohydrate, reduced-energy diet can have beneficial effects on body weight and plasma glucose, habitual high-protein intake, without marked carbohydrate and energy restriction, is associated with increased cardiometabolic disease risk, presumably mediated by the changes in the hormonal milieu after high-protein intake.

The Effects of High-Protein Diets on Kidney Health and Longevity.

Although high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with-and perhaps without-impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD. The quality of dietary protein may also play a role in kidney health. Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies, including the Singapore Chinese Health Study. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. In light of such findings, adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease. Given the possibility of residual confounding within some observational studies and the conflicting evidence from previous trials, long-term studies including those with large sample sizes are warranted to better ascertain the effects of high protein intake on kidney health.

High Protein Intake Among Preschoolers in Childcare in a Region at Elevated Risk for Obesity.

OBJECTIVES: To compare diet quality of convenience samples of children 2-3 and 4-5 years attending 11 of 75 childcare centers in Hays County, Texas to a nationally representative sample, as part of a needs assessment to inform a childcare center-based intervention. METHODS: Parents completed 24-h recalls of their child's diet in 2014. Usual dietary intake of the regional and age-matched sample from the National Health and Nutrition Examination Survey (2011-2014) was estimated using the National Cancer Institute method. Diet quality was assessed using the Healthy Eating Index. Quantile regression and t-tests compared nutrient intake and Healthy Eating Index scores between the two samples. RESULTS: Children ages 2-3 and 4-5 years in the regional sample (n = 124) consumed a higher percent of calories from protein (19%) than children in the national sample (n = 1613; 14%, P < .0.0001). In the regional sample, 21% of children 2-3 years consumed protein in excess of the AMDR compared to fewer than 1% of children in the national sample. CONCLUSIONS FOR PRACTICE: Assessing regional diet while planning health outreach is important. Among children in childcare in this community, high protein intake may contribute to weight disparity. Workshops with childcare center staff to address center policies, environments, and parent outreach could address replacing some high-protein foods with other nutrient-rich foods.

Refined grains intake in high fat, high protein, low carbohydrate and low energy levels subgroups and higher likelihood of abdominal obesity in Chinese population.

The purpose of this study was to investigate the association between refined grains intake and obesity in China. Refined grain intake was considered in relation to energy intake and at varied levels of macronutrient distribution. A cross-sectional study of 6913 participants was conducted using internet-based dietary questionnaire for Chinese (IDQC). The associations and dose-response relationships between refined grains intake and obesity were investigated using multivariable logistic regression analyses and restricted cubic spline (RCS) models. There was a positive association between refined grains intake and abdominal obesity for all participants (forth quartile OR, 1.313; 95% CI, 1.103-1.760; p < .05) and this association persisted in low energy, low carbohydrate, high fat and high protein level subgroups. A range of favourable refined grains intake was 88-116 g/d (3-4 servings/d), which might decrease the likelihood of obesity for Chinese residents. Further prospective studies are needed to confirm these findings.

High-Protein Diet Induces Hyperuricemia in a New Animal Model for Studying Human Gout.

Hyperuricemia is a central risk factor for gout and increases the risk for other chronic diseases, including cardiometabolic disease, kidney disease, and hypertension. Overproduction of urate is one of the main reasons for hyperuricemia, and dietary factors including seafoods, meats, and drinking are contributed to the development of it. However, the lack of a suitable animal model for urate metabolism is one of the main reasons for the delay and limitations of hyperuricemia research. Combining evolutionary biological studies and clinical studies, we conclude that chicken is a preferred animal model for hyperuricemia. Thus, we provided chickens a high-protein diet (HPD) to evaluate the changes in the serum urate levels in chickens. In our study, the HPD increased the serum urate level and maintained it at a long-term high level in chickens. Long-term high serum urate levels induced an abnormal chicken claw morphology and the precipitation of monosodium urate (MSU) in joint synovial fluid. In addition, a long-term HPD also decreased the glomerular filtration rate and induced mild renal injury. Most importantly, allopurinol and probenecid displayed the positive effects in decreasing serum urate and then attenuated hyperuricemia in chicken model. These findings provide a novel model for hyperuricemia and a new opportunity to further investigate the effects of long-term hyperuricemia on other metabolic diseases.

Perinatal exposure of rats to a maternal diet with varying protein quantity and quality affects the risk of overweight in female adult offspring.

The maternal protein diet during the perinatal period can program the health of adult offspring. This study in rats evaluated the effects of protein quantity and quality in the maternal diet during gestation and lactation on weight and adiposity in female offspring. Six groups of dams were fed a high-protein (HP; 47% protein) or normal-protein (NP; 19% protein) isocaloric diet during gestation (G) using either cow's milk (M), pea (P) or turkey (T) proteins. During lactation, all dams received the NP diet (protein source unchanged). From postnatal day (PND) 28 until PND70, female pups (n=8) from the dam milk groups were exposed to either an NP milk diet (NPMW) or to dietary self-selection (DSS). All other pups were only exposed to DSS. The DSS design was a choice between five food cups containing HPM, HPP, HPT, carbohydrates or lipids. The weights and food intakes of the animals were recorded throughout the study, and samples from offspring were collected on PND70. During the lactation and postweaning periods, body weight was lower in the pea and turkey groups (NPG and HPG) versus the milk group (P<.0001). DSS groups increased their total energy and fat intakes compared to the NPMW group (P<.0001). In all HPG groups, total adipose tissue was increased (P=.03) associated with higher fasting plasma leptin (P<.05). These results suggest that the maternal protein source impacted offspring body weight and that protein excess during gestation, irrespective of its source, increased the risk of adiposity development in female adult offspring.

High Dietary Protein Does Not Alter Renal Prostanoids and Other Oxylipins in Normal Mice or in Those with Inherited Kidney Disease.

BACKGROUND: Ex vivo studies suggest that increased renal prostanoids can mediate effects of high-protein (HP) compared with low-protein (LP) diets on normal and diseased kidneys. However, a short-term HP feeding study in normal male rats failed to demonstrate higher renal prostanoids in vivo. OBJECTIVES: The aim of the present study was to investigate whether long-term HP feeding alters renal prostanoids in male and female mice, with and without kidney disease. METHODS: Weanling normal mice (CD1) and mice with kidney disease (CD1-pcy/pcy mice) were fed standard diets with normal protein [NP, 20% of energy (%E)] or HP (35%E) for 13 wk. Renal disease was assessed by histomorphometric analysis of cysts and fibrosis, and measurement of serum urea nitrogen (SUN) and creatinine concentrations. Targeted analysis of renal oxylipins was performed by HPLC-MS/MS. RESULTS: The HP diet increased kidney size and water content of normal kidneys, and worsened disease in CD1-pcy/pcy mice as indicated by higher (P < 0.05) kidney weights (8-31%), water content (8-10%), cyst volume (36-60%), fibrous volume (44-53%), and SUN (47-55%). Diseased compared with normal kidneys had higher (P < 0.05) concentrations of 6 of 11 prostanoids and lower (P < 0.05) concentrations of 33 of 54 other oxylipins. This is consistent with previously known effects of dietary HP and disease effects on the kidney. However, the HP diet did not alter renal prostanoids and other renal oxylipins in either normal or diseased kidneys (P < 0.05), despite having the expected physiological effects on normal and diseased kidneys. This study also showed that females have higher concentrations of renal prostanoids [9 of 11 prostanoids higher (P < 0.05) in females], but lower concentrations of other oxylipins [28 of 54 other oxylipins lower (P < 0.05) in females]. CONCLUSIONS: The effects of HP diets on normal and diseased kidneys in CD1 and CD1-pcy/pcy mice are independent of renal oxylipin alterations.