The influence of substituting dietary peptide-bound with free amino acids on nitrogen metabolism and acid-base balance of broiler chickens depends on asparagine and glutamine supply.

Reducing dietary crude protein (CP) concentration while maintaining adequate amino acid (AA) supply by free AA inclusion can contribute to attenuate the negative environmental effects of animal farming. This study investigated upper limits of dietary free AA inclusions without undesirable effects including the dependence on asparagine (Asn) and glutamine (Gln) supply. Ten broilers were allocated to sixty-three metabolism units each and offered nine experimental diets from day (d) 7-21 (n 7). One diet (167 g CP/kg) contained 80 g soya protein isolate (SPI)/kg. In the other diets, 25, 50, 75 and 100 % of the digestible AA from SPI were substituted with free AA. Digestible Asn+aspartic acid (Asp) and Gln+glutamic acid (Glu) were substituted with Asp/Glu or 50/50 mixes of Asp/Asn and Glu/Gln, respectively. Total excreta were collected from d 11-14 and from d 18-21. Growth and nitrogen accretion were unaffected by 25 and 50 % substitution without and with free Asn/Gln, respectively, but decreased at higher substitution (P ≤ 0·024). Circulating concentrations of Asp, Glu and Gln were unaffected by treatment, while Asn decreased at substitution higher than 50 % when Asn/Gln were not provided (P ≤ 0·005). Blood gas analysis on d 21 indicated a compensated metabolic acidosis at substitution higher than 50 and 75 % without and with free Asn/Gln, respectively (P ≤ 0·017). Results suggest that adding Asn/Gln increased an upper limit for proportion of dietary free AA from 10 to 19 % of dietary CP and enabled higher free AA inclusion without affecting the acid-base balance.

Can dietary proteins selectively reduce either the visceral or subcutaneous adipose tissues?

There is a considerable appeal for interventions that can selectively reduce either the visceral or subcutaneous white adipose tissues in humans and other species because of their associated impact on outcomes related to metabolic health. Here, we reviewed the data related to the specificity of five interventions to affect the two depots in humans and rodents. The interventions relate to the use of dietary proteins, monounsaturated fatty acids, polyunsaturated fatty acids, calorie restriction, or bariatric surgery. The available data show that calorie restriction and bariatric surgery reduce both visceral and subcutaneous tissues, whereas there is no consistency in the effect of monounsaturated or polyunsaturated fatty acids. Dietary proteins, more specifically, whey proteins show efficacy to reduce one or both depots based on how the proteins interact with other macronutrients in the diet. We provide evidence that this specificity is related to changes in the composition and the functional potential of the gut microbiota and the resulting metabolites produced by these microorganisms. The effect of the sex of the host is also discussed. This knowledge may help to develop nutritional approaches to deplete either the visceral or subcutaneous adipose tissues and improve metabolic health in humans and other species.

Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21.

Fibroblast growth factor 21 (FGF21), a hormone predominantly released in the liver, has emerged as a critical endocrine signal of dietary protein intake, but its role in the control of estrous cyclicity by dietary protein remains uncertain. To investigated the role of FGF21 and hypothalamic changes in the regulation of estrous cyclicity by dietary protein intake, female adult Sprague-Dawley rats with normal estrous cycles were fed diets with protein contents of 4% (P4), 8% (P8), 13% (P13), 18% (P18), and 23% (P23). FGF21 liver-specific knockout or wild-type mice were fed P18 or P4 diets to examine the role of liver FGF21 in the control of estrous cyclicity. Dietary protein restriction resulted in no negative effects on estrous cyclicity or ovarian follicular development when the protein content was greater than 8%. Protein restriction at 4% resulted in decreased bodyweight, compromised Kiss-1 expression in the hypothalamus, disturbed estrous cyclicity, and inhibited uterine and ovarian follicular development. The disturbed estrous cyclicity in rats that received the P4 diet was reversed after feeding with the P18 diet. Liver Fgf21 mRNA expressions and serum FGF21 levels were significantly increased as dietary protein content decreased, and loss of hepatic FGF21 delayed the onset of cyclicity disruption in rats fed with the P4 diet, possibly due to the regulation of insulin-like growth factor-1. Collectively, severe dietary protein restriction results in the cessation of estrous cyclicity and ovarian follicle development, and hepatic FGF21 and hypothalamic Kiss-1 were partially required for this process.

Reprogramming tumour-associated macrophages to outcompete cancer cells.

In metazoan organisms, cell competition acts as a quality control mechanism to eliminate unfit cells in favour of their more robust neighbours1,2. This mechanism has the potential to be maladapted, promoting the selection of aggressive cancer cells3-6. Tumours are metabolically active and are populated by stroma cells7,8, but how environmental factors affect cancer cell competition remains largely unknown. Here we show that tumour-associated macrophages (TAMs) can be dietarily or genetically reprogrammed to outcompete MYC-overexpressing cancer cells. In a mouse model of breast cancer, MYC overexpression resulted in an mTORC1-dependent 'winner' cancer cell state. A low-protein diet inhibited mTORC1 signalling in cancer cells and reduced tumour growth, owing unexpectedly to activation of the transcription factors TFEB and TFE3 and mTORC1 in TAMs. Diet-derived cytosolic amino acids are sensed by Rag GTPases through the GTPase-activating proteins GATOR1 and FLCN to control Rag GTPase effectors including TFEB and TFE39-14. Depletion of GATOR1 in TAMs suppressed the activation of TFEB, TFE3 and mTORC1 under the low-protein diet condition, causing accelerated tumour growth; conversely, depletion of FLCN or Rag GTPases in TAMs activated TFEB, TFE3 and mTORC1 under the normal protein diet condition, causing decelerated tumour growth. Furthermore, mTORC1 hyperactivation in TAMs and cancer cells and their competitive fitness were dependent on the endolysosomal engulfment regulator PIKfyve. Thus, noncanonical engulfment-mediated Rag GTPase-independent mTORC1 signalling in TAMs controls competition between TAMs and cancer cells, which defines a novel innate immune tumour suppression pathway that could be targeted for cancer therapy.

Intermittent protein restriction improves glucose homeostasis in Zucker diabetic fatty rats and single-cell sequencing reveals distinct changes in ß cells.

Diabetes is caused by the interplay between genetic and environmental factors, therefore changes of lifestyle and dietary patterns are the most common practices for diabetes intervention. Protein restriction and caloric restriction have been shown to improve diabetic hyperglycemia in both animal models and humans. We report here the effectiveness of intermittent protein restriction (IPR) for the intervention of diabetes in Zucker diabetic fatty (ZDF) rats. Administration of IPR significantly reduced hyperglycemia and decreased glucose production in the liver. IPR protected pancreatic islets from diabetes-mediated damages as well as elevated the number and the proliferation activity of ß cells. Single-cell RNA sequencing performed with isolated islets from the ZDF rats revealed that IPR was able to reverse the diabetes-associated ß cell dedifferentiation. In addition, diabetic ß cells in ZDF rats were associated with increased expressions of islet amyloid polypeptide, chromogranin and genes involved in endoplasmic reticulum stress. A ß cell dedifferentiation marker Cd81 was also increased in the ß cells of diabetic rats. In contrast, the expressions of D-box binding PAR bZIP transcription factor Dbp and immediate-early response genes were reduced in the diabetic ß cells. In conclusion, these results indicated that IPR is effective in glycemic control and ß cell protection in a diabetic rat model. In addition, diabetes in ZDF rats is associated with changes in the expression of genes involved in many facets of ß cell functions.

Protein intake and bone mineral density: Cross-sectional relationship and longitudinal effects in older adults.

BACKGROUND: There are several mechanisms via which increased protein intake might maintain or improve bone mineral density (BMD), but current evidence for an association or effect is inconclusive. The objectives of this study were to investigate the association between dietary protein intake (total, plant and animal) with BMD (spine and total body) and the effects of protein supplementation on BMD. METHODS: Individual data from four trials that included either (pre-)frail, undernourished or healthy older adults (aged ≥65 years) were combined. Dietary intake was assessed with food records (2, 3 or 7 days) and BMD with dual-energy X-ray absorptiometry (DXA). Associations and effects were assessed by adjusted linear mixed models. RESULTS: A total of 1570 participants [57% women, median (inter-quartile range): age 71 (68-75) years] for which at least total protein intake and total body BMD were known were included in cross-sectional analyses. In fully adjusted models, total protein intake was associated with higher total body and spine BMD [beta (95% confidence interval): 0.0011 (0.0006-0.0015) and 0.0015 (0.0007-0.0023) g/cm2 , respectively]. Animal protein intake was associated with higher total body and spine BMD as well [0.0011 (0.0007-0.0016) and 0.0017 (0.0010-0.0024) g/cm2 , respectively]. Plant protein intake was associated with a lower total body and spine BMD [-0.0010 (-0.0020 to -0.0001) and -0.0019 (-0.0034 to -0.0004) g/cm2 , respectively]. Associations were similar between sexes. Participants with a high ratio of animal to plant protein intake had higher BMD. In participants with an adequate calcium intake and sufficient serum 25(OH)D concentrations, the association between total protein intake with total body and spine BMD became stronger. Likewise, the association between animal protein intake with total body BMD was stronger. In the longitudinal analyses, 340 participants [58% women, median (inter-quartile range): age 75 (70-81) years] were included. Interventions of 12 or 24 weeks with protein supplementation or protein supplementation combined with resistance exercise did not lead to significant improvements in BMD. CONCLUSIONS: An association between total and animal protein intake with higher BMD was found. In contrast, plant protein intake was associated with lower BMD. Research is warranted to further investigate the added value of dietary protein alongside calcium and vitamin D for BMD improvement, especially in osteopenic or osteoporotic individuals. Moreover, more research on the impact of a plant-based diet on bone health is needed.

Effects of dietary protein content and crystalline amino acid supplementation patterns on growth performance, intestinal histomorphology, and immune response in weaned pigs raised under different sanitary conditions.

The aim of this experiment was to investigate the effects of dietary crude protein (CP) contents and crystalline amino acids (CAA) supplementation patterns on growth performance, intestinal histomorphology, and immune response in weaned pigs under clean (CSC) or unclean sanitary conditions (USC). A total of 144 weaned pigs (6.35 ± 0.63 kg body weight) were assigned to 6 treatments in a 3 × 2 factorial arrangement based on CP content and sanitary conditions using a randomized complete block design, giving 8 replicates per treatment with 3 pigs per pen. Pigs were fed one of three diets for 21 d: one high CP (HCP; 22%) and two low CP (LCP; 19%) diets supplemented with 9 indispensable AA or only 6 AA (Lys, Met, Thr, Trp, Val, and Ile) as CAA. The CSC room was washed weekly, whereas the USC room had sow manure spread in the pens and was not washed throughout the experiment. Body weight and feed disappearance were recorded weekly. Blood was sampled from 1 pig per pen weekly, and the same pig was euthanized for jejunal tissues sampling on day 21. Pigs raised under USC had reduced (P < 0.05) average daily gain (ADG) and gain to feed ratio (G:F) in week 2, but contrary results that greater (P < 0.05) ADG and G:F were found in pigs under USC in week 3. Overall, there was an interaction where G:F did not differ between HCP and LCP under CSC, however, LCP decreased (P < 0.05) G:F compared to HCP under USC. Pigs fed the HCP diet had higher (P < 0.05) fecal scores than those fed the LCP diets throughout the experiment. Pigs fed the LCP had higher (P < 0.05) villus height to crypt depth ratio than those fed the HCP. An interaction was observed where goblet cell density in the jejunum was higher (P < 0.05) in pigs fed LCP than HCP under CSC, but no difference was found between HCP and LCP under USC. Different CAA supplementation patterns did not influence both growth performance and histomorphology. Pigs raised under USC had greater (P < 0.05) plasma interleukin (IL)-10 and IL-6 concentrations and reduced (P < 0.05) plasma tumor necrosis factor-alpha concentration. Also, the LCP diets resulted in a greater (P < 0.05) plasma IL-10 concentration. In conclusion, overall growth performance did not differ between HCP and LCP under CSC, but LCP diets reduced G:F under USC. Feeding LCP diets to weaned pigs improved gut morphology under USC and ameliorated systemic inflammation induced by USC, whereas CAA supplementation patterns did not affect growth performance and gut morphology.

Reducing dietary crude protein (CP) content reduces nitrogen excretion to the environment and undigested protein availability to enteric pathogens in the hind gut resulting in reduced postweaning diarrhea and improved gut health. To meet the amino acid requirements in low CP diets, supplementation of essential amino acids in nursery diets is necessary, and the availability of more feed-grade crystalline amino acids allows low CP diets to be practically formulated. The sanitation challenge model mimics commercial raising conditions and stimulates a low-grade inflammatory and immune response. Although low CP diets decreased the feed efficiency in pigs raised under unclean conditions in this study, improved gut histomorphology and ameliorated inflammatory response were obtained in pigs fed low CP diets. However, no effect was found in crystalline amino acids supplementation patterns. The outcomes of this study confirmed that low CP diets could be used to improve gut health and ameliorate immune response in weaned pigs.

Low-protein diet is inversely related to the incidence of chronic kidney disease in middle-aged and older adults: results from a community-based prospective cohort study.

PURPOSE: Dietary protein intake can modulate renal health. However, the effect of dietary protein restriction on kidney function in the general population remains unclear. This study aimed to examine the association between total protein intake and new-onset chronic kidney disease (CKD) in Korean adults. METHODS: We included 7339 participants from the Korean Genome and Epidemiology Study. Participants were divided into low-protein diet (LPD, < 0.8 g/kg/day), normal-protein diet (NPD, 0.8-1.3 g/kg/day), and high-protein diet (HPD, > 1.3 g/kg/day) groups. New-onset CKD was defined as two consecutive events of estimated glomerular filtration rate < 60 mL/min/1.73 m2. Multivariable Cox hazard regression analysis was conducted to examine the association of total protein intake with new-onset CKD. Subgroup analyses according to diabetes mellitus (DM) status were performed. We performed the same analyses by dividing participants into total protein, plant protein, and animal protein intake tertiles. RESULTS: During a median follow-up of 13.7 years, 633 (8.7%) participants newly developed CKD. The fully adjusted hazard ratios (HR) with 95% confidence interval (CI) for incident CKD of the LPD and HPD groups compared with the NPD group were 1.49 (1.18-1.87) and 0.63 (0.45-0.87), respectively. The HR (95% CI) of the highest tertile group of plant protein intake for incident CKD was 0.72 (0.54-0.93), compared with that of the lowest tertile group. Similar trends were observed only in the non-DM subgroup, not in the DM subgroup. CONCLUSION: Protein intake, especially plant proteins, was negatively associated with the incidence of new-onset CKD in middle-aged and older Korean adults.

Effects of corn distillers grains with yeast bodies and manipulation of dietary cation and anion difference on production, nutrient digestibility, and gas emissions from manure in lactating cows.

In a randomized complete block design, 40 lactating Holstein cows (average 98 d in milk and 41 kg/d of milk yield) were randomly assigned to 1 of 4 diets: (1) containing soybean meal as the major protein supplement (CON diet); (2) CON diet with high-protein dried corn distillers grains at 20% on a dry matter (DM) basis by replacing mainly soybean meal (DG diet); (3) DG diet except that high-protein dried corn distillers grains with yeast bodies (extracted after corn ethanol production) was used (DGY diet); or (4) DG diet supplemented with sodium bicarbonate and potassium carbonate to elevate the dietary cation and anion difference (DCAD; DG-DCAD diet). The DCAD of CON, DG, DGY, and DG-DCAD were 185, 62, 67, and 187 mEq/kg of DM, respectively. The experiment began with a 10-d covariate period and then cows were fed the experimental diets for 5 wk (2-wk diet adaptation and 3-wk data collection periods). Dry matter intake and milk yield were measured daily, and spot urine and fecal samples were collected in the last week of the experiment to measure nutrient digestibility; N, S, and P utilization and excretion; and in vitro NH3 and H2S emissions from manure. All data were analyzed using the MIXED procedure of SAS (random effect: block; fixed effects: diets, repeated week, and interactions). During data collection, DM intake was not different among treatment groups, but milk yield tended to be lower (42.4 vs. 39.9 kg/d) for DG, DGY, and DG-DCAD versus CON, which could have been caused by decreases in organic matter and neutral detergent fiber digestibility. Milk protein yield tended to be lower (1.33 vs. 1.24 kg/d) for DG, DGY, and DG-DCAD versus CON. Milk fat yield was lower (1.26 vs. 1.55 kg/d) for DG and DGY versus CON, but that for DG-DCAD (1.43 kg/d) did not differ from CON. Similarly, energy-corrected milk was lower (38.0 vs. 43.3 kg/d) for cows on DG and DGY versus those on CON, but it did not differ between DG-DCAD (40.7 kg/d) and CON. Urinary and fecal N excretion were greater for DG, DGY, and DG-DCAD compared with CON due to greater dietary crude protein content and N intake. However, NH3 emissions did not differ across treatments. Intakes of dietary P and S were greater for DG, DGY, and DG-DCAD, resulting in greater excretion of those in manure and greater H2S emissions from manure compared with CON. These data suggest that the negative effects of feeding distillers grains on production of lactating cows can be partly explained by a decrease in nutrient digestibility (milk yield) and excessive anion load (milk fat). The milk fat response to DG-DCAD suggests that milk fat depression observed with a diet with high content of distillers grains can be partially alleviated by supplementation of cations. In the current study, we observed no beneficial effects of DG containing yeast bodies.

Role of ACE2-Ang (1-7)-Mas axis in post-COVID-19 complications and its dietary modulation.

Severe acute respiratory syndrome-coronavirus-2 (COVID-19) virus uses Angiotensin-Converting Enzyme 2 (ACE2) as a gateway for their entry into the human body. The ACE2 with cleaved products have emerged as major contributing factors to multiple physiological functions and pathogenic complications leading to the clinical consequences of the COVID-19 infection Decreased ACE2 expression restricts the viral entry into the human cells and reduces the viral load. COVID-19 infection reduces the ACE2 expression and induces post-COVID-19 complications like pneumonia and lung injury. The modulation of the ACE2-Ang (1-7)-Mas (AAM) axis is also being explored as a modality to treat post-COVID-19 complications. Evidence indicates that specific food components may modulate the AAM axis. The variations in the susceptibility to COVID-19 infection and the post-COVID its complications are being correlated with varied dietary habits. Some of the food substances have emerged to have supportive roles in treating post-COVID-19 complications and are being considered as adjuvants to the COVID-19 therapy. It is possible that some of their active ingredients may emerge as the direct treatment for the COVID-19.

Improved Healing after Non-Surgical Periodontal Therapy Is Associated with Higher Protein Intake in Patients Who Are Non-Smokers.

The aim of this study was to determine whether a relationship between periodontal healing and protein intake exists in patients undergoing non-surgical treatment for periodontitis. Dietary protein intake was assessed using the 2005 Block food frequency questionnaire in patients with chronic generalized periodontitis undergoing scaling and root planing (n = 63 for non-smokers, n = 22 for smokers). Protein intake was correlated to post-treatment probing depth using multiple linear regression. Non-smoking patients who consumed ≥1 g protein/kg body weight/day had fewer sites with probing depth ≥ 4 mm after scaling and root planing compared to patients with intakes <1 g protein/kg body weight/day (11 ± 2 versus 16 ± 2, p = 0.05). This relationship was strengthened after controlling for baseline probing depth, hygienist and time between treatment and follow-up (10 ± 2 versus 16 ± 1, p = 0.018) and further strengthened after controlling for potential confounders including age, sex, body mass index, flossing frequency, and bleeding on probing (8 ± 2 versus 18 ± 2, p < 0.001). No associations were seen in patients who smoked. Consuming ≥1 g protein/kg body weight/day was associated with reductions in periodontal disease burden following scaling and root planing in patients who were non-smokers. Further studies are needed to differentiate between animal and plant proteins.

Dietary Collagen Hydrolysates Ameliorate Furrowed and Parched Skin Caused by Photoaging in Hairless Mice.

Collagen hydrolysates have been suggested as a favorable antiaging modality in skin photoaged by persistent exposure to ultraviolet radiation (UV). The current study evaluated the beneficial effect of collagen hydrolysates (fsCH) extracted from Pangasius hypophthalmus fish skin on wrinkle formation and moisture preservation in dorsal skin of hairless mice challenged with UV-B. Inter-comparative experiments were conducted for anti-photoaging among fsCH, retinoic acid (RA), N-acetyl-D-glucosamine (NAG), and glycine-proline-hydroxyproline (GPH). Treating human HaCaT keratinocytes with 100-200 µg/mL fsCH reciprocally ameliorated the expression of aquaporin 3 (AQP3) and CD44 deranged by UV-B. The UV-B-induced deep furrows and skin thickening were improved in parched dorsal skin of mice supplemented with 206-412 mg/kg fsCH as well as RA and GPH. The UV-B irradiation enhanced collagen fiber loss in the dorsal dermis, which was attenuated by fsCH through enhancing procollagen conversion to collagen. The matrix metalloproteinase expression by UV-B in dorsal skin was diminished by fsCH, similar to RA and GPH, via blockade of collagen degradation. Supplementing fsCH to UV-B-irradiated mice decreased transepidermal water loss in dorsal skin with reduced AQP3 level and restored keratinocyte expression of filaggrin. The expression of hyaluronic acid synthase 2 and hyaluronidase 1 by UV-B was remarkably ameliorated with increased production of hyaluronic acid by treating fsCH to photoaged mice. Taken together, fsCH attenuated photoaging typical of deep wrinkles, epidermal thickening, and skin water loss, like NAG, RA, or GPH, through inhibiting collagen destruction and epidermal barrier impairment.

Energetic and health effects of protein overconsumption constrain dietary adaptation in an apex predator.

Studies of predator feeding ecology commonly focus on energy intake. However, captive predators have been documented to selectively feed to optimize macronutrient intake. As many apex predators experience environmental changes that affect prey availability, limitations on selective feeding can affect energetics and health. We estimated the protein:fat ratio of diets consumed by wild polar bears using a novel isotope-based approach, measured protein:fat ratios selected by zoo polar bears offered dietary choice and examined potential energetic and health consequences of overconsuming protein. Dietary protein levels selected by wild and zoo polar bears were low and similar to selection observed in omnivorous brown bears, which reduced energy intake requirements by 70% compared with lean meat diets. Higher-protein diets fed to zoo polar bears during normal care were concurrent with high rates of mortality from kidney disease and liver cancer. Our results suggest that polar bears have low protein requirements and that limitations on selective consumption of marine mammal blubber consequent to climate change could meaningfully increase their energetic costs. Although bear protein requirements appear lower than those of other carnivores, the energetic and health consequences of protein overconsumption identified in this study have the potential to affect a wide range of taxa.

Whey protein preload enhances the active GLP-1 response and reduces circulating glucose in women with polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) increases risk for development of type 2 diabetes. Whey protein ingestion before a carbohydrate load attenuates blood glucose. For our exploratory, case-control study design, we hypothesized that 35 g whey protein isolate (WPI) preloading would increase postprandial incretins and reduce hyperglycemia in women with PCOS. Twenty-nine age-matched women (PCO = 14 and CON = 15) completed oral glycemic tolerance tests (OGTT) following baseline (Day 0) as well as 35 g WPI acute (Day 1) and short-term supplementation (Day 7). Eight venous samples were collected during each test for quantification of glucose, and enteropancreatic hormones and to calculate area under the curve (AUC). Data was analyzed via repeated measures ANCOVA with significance set at P< .05. "Day x time x group" significantly influenced glucose (P = .01) and insulin changes (P = .03). In both groups, AUCglu were significantly lower on Day 7 than Day 0 (P< .05). Postprandial glucose excursions were lower on Days 1 and 7 than Day 0 in PCO and CON. Both, PCO and CON exhibited greater insulin changes on Days 1 and 7 compared to Day 0 (P< .05). AUCglucagon were higher on Days 1 and 7 than on Day 0 (P< .05). Changes in active GLP-1 were higher on Day 1 than Day 0 (P= .03). Overall, we showed that WPI preloading augmented insulin release and consequently lowered circulating glucose in women with and without PCOS. This insulinogenic effect can be attributed to enhanced active GLP-1 levels. We concluded that the incretin-mimetic effect of WPI may aid women with PCOS in achieving glycemic homeostasis.

Urinary Dopamine Excretion Rate Decreases during Acute Dietary Protein Deprivation and Is Associated with Increased Plasma Pancreatic Polypeptide Concentration.

Background: Dopamine, a key neurotransmitter in the autonomic nervous system participating in the homeostatic balance between sympathetic and parasympathetic divisions, is involved in food intake regulation. Objective: We investigated whether dopamine is altered by acute fasting or overfeeding diets with varying macronutrient content. Design: Ninety-nine healthy subjects underwent 24-h dietary interventions including eucaloric feeding, fasting, and five different overfeeding diets in a crossover design. Overfeeding diets (200% of eucaloric requirements) included one diet with 3%-protein (low-protein high-fat overfeeding-LPF: 46%-fat), three diets with 20%-protein, and a diet with 30%-protein (44%-fat). Urine was collected for 24 h and urinary dopamine concentration was quantified by high-performance liquid chromatography. Plasma pancreatic polypeptide (PP) concentration, an indirect marker of parasympathetic activity, was measured prior to and after each diet after an overnight fast. Results: During 24-h of fasting, dopamine decreased on average by ~14% compared to eucaloric conditions, whereas PP increased by two-fold (both p < 0.001). Lower dopamine during 24-h fasting correlated with increased PP (r = -0.40, p < 0.001). Similarly, on average urinary dopamine decreased during LPF by 14% (p < 0.001) and lower dopamine correlated with increased PP (r = -0.31, p = 0.01). No changes in dopamine and PP concentrations were observed during other overfeeding diets (all p > 0.05). Conclusions: Dopamine concentrations decrease during short-term fasting and overfeeding with a low-protein diet. As both dietary conditions have in common protein deficit, the correlation between dopamine and PP suggests a compensatory mechanism underlying the shift from sympathetic to parasympathetic drive during dietary protein deprivation.

Association of Major Dietary Protein Sources With All-Cause and Cause-Specific Mortality: Prospective Cohort Study.

Background Dietary recommendations regarding protein intake have been focused on the amount of protein. However, such recommendations without considering specific protein sources may be simplistic and insufficient. Methods and Results We included 102 521 postmenopausal women enrolled in the Women's Health Initiative between 1993 and 1998, and followed them through February 2017. During 1 876 205 person-years of follow-up, 25 976 deaths occurred. Comparing the highest with the lowest quintile, plant protein intake was inversely associated with all-cause mortality (hazard ratio [HR], 0.91 [0.86, 0.96]), cardiovascular disease mortality (HR, 0.88 [0.79, 0.97]), and dementia mortality (HR, 0.79 [0.67, 0.94]). Among major protein sources, comparing the highest with the lowest quintile of consumption, processed red meat (HR, 1.06 [1.01, 1.10]) or eggs (HR, 1.14 [1.10, 1.19]) was associated with higher risk of all-cause mortality. Unprocessed red meat (HR, 1.12 [1.02, 1.23]), eggs (HR, 1.24 [1.14, 1.34]), or dairy products (HR, 1.11 [1.02, 1.22]) was associated with higher risk of cardiovascular disease mortality. Egg consumption was associated with higher risk of cancer mortality (HR, 1.10 [1.02, 1.19]). Processed red meat consumption was associated with higher risk of dementia mortality (HR, 1.20 [1.05, 1.32]), while consumption of poultry (HR, 0.85 [0.75, 0.97]) or eggs (HR, 0.86 [0.75, 0.98]) was associated with lower risk of dementia mortality. In substitution analysis, substituting of animal protein with plant protein was associated with a lower risk of all-cause mortality, cardiovascular disease mortality, and dementia mortality, and substitution of total red meat, eggs, or dairy products with nuts was associated with a lower risk of all-cause mortality. Conclusions Different dietary protein sources have varying associations with all-cause mortality, cardiovascular disease mortality, and dementia mortality. Our findings support the need for consideration of protein sources in future dietary guidelines.

Effect of Overeating Dietary Protein at Different Levels on Circulating Lipids and Liver Lipid: The PROOF Study.

BACKGROUND: During overeating, a low protein diet slowed the rate of weight gain and increased the energy cost of the added weight, suggesting that low protein diets reduced energy efficiency. The Protein Overfeeding (PROOF) study explored the metabolic changes to low and high protein diets, and this sub-study examined the changes in body composition and blood lipids when eating high and low protein diets during overeating. METHODS: Twenty-three healthy volunteers (M = 14; F = 9) participated in an 8-week, parallel arm study where they were overfed by ~40% with diets containing 5% (LPD = low protein diet), 15% (NPD = normal protein diet), or 25% (HPD = high protein diet) protein. Dual energy X-ray absorptiometry (DXA) and computer tomography (CT) were used to quantify whole body and abdominal fat and intrahepatic lipid, respectively. Metabolites were measured by standard methods. RESULTS: Protein intake and fat intake were inversely related since carbohydrate intake was fixed. Although overeating the LPD diet was associated with a significant increase in high density lipoprotein (HDL)-cholesterol (p < 0.001) and free fatty acids (p = 0.034), and a significant decrease in fat free mass (p < 0.0001) and liver density (p = 0.038), statistical models showed that dietary protein was the main contributor to changes in fat free mass (p = 0.0040), whereas dietary fat was the major predictor of changes in HDL-cholesterol (p = 0.014), free fatty acids (p = 0.0016), and liver fat (p = 0.0007). CONCLUSIONS: During 8 weeks of overeating, the level of dietary protein intake was positively related to the change in fat free mass, but not to the change in HDL-cholesterol, free fatty acids, and liver fat which were, in contrast, related to the intake of dietary fat.

Dietary Protein Intake and Single-Nephron Glomerular Filtration Rate.

High protein intake can increase glomerular filtration rate (GFR) in response to excretory overload, which may exacerbate the progression of kidney disease. However, the direct association between glomerular hemodynamic response at the single-nephron level and dietary protein intake has not been fully elucidated in humans. In the present study, we evaluated nutritional indices associated with single-nephron GFR (SNGFR) calculated based on corrected creatinine clearance (SNGFRCr). We retrospectively identified 43 living kidney donors who underwent enhanced computed tomography and kidney biopsy at the time of donation at Jikei University Hospital in Tokyo from 2007 to 2018. Total nephron number was estimated with imaging-derived cortical volume and morphometry-derived glomerular density. SNGFRCr was calculated by dividing the corrected creatinine clearance by the number of non-sclerosed glomeruli (NglomNSG). The mean (± standard deviation) NglomNSG/kidney and SNGFRCr were 685,000 ± 242,000 and 61.0 ± 23.9 nL/min, respectively. SNGFRCr was directly associated with estimated protein intake/ideal body weight (p = 0.005) but not with body mass index, mean arterial pressure, albumin, or sodium intake. These findings indicate that greater protein intake may increase SNGFR and lead to glomerular hyperfiltration.

Effect of carbohydrate-protein supplementation on endurance training adaptations.

PURPOSE: To examine the influence of post-exercise protein feeding upon the adaptive response to endurance exercise training. METHODS: In a randomised parallel group design, 25 healthy men and women completed 6 weeks of endurance exercise training by running on a treadmill for 30-60 min at 70-75% maximal oxygen uptake (VO2max) 4 times/week. Participants ingested 1.6 g per kilogram of body mass (g kg BM-1) of carbohydrate (CHO) or an isocaloric carbohydrate-protein solution (CHO-P; 0.8 g carbohydrate kg BM-1 + 0.8 g protein kg BM-1) immediately and 1 h post-exercise. Expired gas, blood and muscle biopsy samples were taken at baseline and follow-up. RESULTS: Exercise training improved VO2max in both groups (p ≤ 0.001), but this increment was not different between groups either in absolute terms or relative to body mass (0.2 ± 0.2 L min-1 and 3.0 ± 2 mL kg-1 min-1, respectively). No change occurred in plasma albumin concentration from baseline to follow-up with CHO-P (4.18 ± 0.18 to 4.23 ± 0.17 g dL-1) or CHO (4.17 ± 0.17 to 4.12 ± 0.22 g dL-1; interaction: p > 0.05). Mechanistic target of rapamycin (mTOR) gene expression was up-regulated in CHO-P (+ 46%; p = 0.025) relative to CHO (+ 4%) following exercise training. CONCLUSION: Post-exercise protein supplementation up-regulated the expression of mTOR in skeletal muscle over 6 weeks of endurance exercise training. However, the magnitude of improvement in VO2max was similar between groups.

Dietary protein and appetite sensations in individuals with overweight and obesity: a systematic review.

PURPOSE: This systematic review aimed to synthesize the available evidence on the effects of a high-protein diet on appetite sensations in individuals with overweight and obesity. METHODS: Two authors independently conducted literature searches, study selection, design of the method, and quality appraisal. The main inclusion criteria were studies involving protocols that present a protein intake greater than 1.2 g/kg/day or 25% of the total daily energy content compared to a normal protein diet, i.e., 0.8-1.2 g/kg/day or 15%-20% of the total energy content. Studies that evaluated test meals or diet within a period of less than 7 days and participants with diabetes, cancer, or other specific conditions were excluded from this review. The literature search was updated until November 2019 using the main databases available. RESULTS: Of a total of 4191 records, ten articles met the inclusion criteria and included a total of 1079 subjects. In six studies, participants experienced enhanced fullness or satiety in response to a high-dietary protein intake, of which four studies had an intervention period of 10-12 weeks. CONCLUSION: Our results suggest that among individuals with overweight or obesity, higher dietary protein intake may influence appetite sensations by enhancing fullness or satiety. The low level of evidence, due to the heterogeneity of the protocols and the high risk of bias, highlights the need for further studies to confirm these results.