scholarly journals Colorectal Cancer Progression Is Potently Reduced by a Glucose-Free, High-Protein Diet: Comparison to Anti-EGFR Therapy

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5817
Author(s):  
Kerstin Skibbe ◽  
Ann-Kathrin Brethack ◽  
Annika Sünderhauf ◽  
Mohab Ragab ◽  
Annika Raschdorf ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cancer Progression ◽  
Goblet Cell ◽  
Aerobic Glycolysis ◽  
Control Diet ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
High Amino Acid ◽  
Goblet Cell Differentiation

To enable rapid proliferation, colorectal tumor cells up-regulate epidermal growth factor receptor (EGFR) signaling and aerobic glycolysis, resulting in substantial lactate release into the tumor microenvironment and impaired anti-tumor immune responses. We hypothesized that a nutritional intervention designed to reduce aerobic glycolysis may boost the EGFR-directed antibody (Ab)-based therapy of pre-existing colitis-driven colorectal carcinoma (CRC). CRC development was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) administration to C57BL/6 mice. AOM/DSS-treated mice were fed a glucose-free, high-protein diet (GFHPD) or an isoenergetic control diet (CD) in the presence or absence of an i.p. injection of an anti-EGFR mIgG2a or respective controls. AOM/DSS-treated mice on a GFHPD displayed a reduced systemic glucose metabolism associated with reduced oxidative phosphorylation (OXPHOS) complex IV expression and diminished tumor loads. Comparable but not additive to an anti-EGFR-Ab therapy, the GFHPD was accompanied by enhanced tumoral goblet cell differentiation and decreased colonic PD-L1 and splenic CD3e, as well as PD-1 immune checkpoint expression. In vitro, glucose-free, high-amino acid culture conditions reduced proliferation but improved goblet cell differentiation of murine and human CRC cell lines MC-38 and HT29-MTX in combination with down-regulation of PD-L1 expression. We here found GFHPD to systemically dampen glycolysis activity, thereby reducing CRC progression with a similar efficacy to EGFR-directed antibody therapy.

scholarly journals Colorectal cancer progression is potently reduced by a glucose-free, high-protein diet: comparison to anti-EGFR therapy

2021 ◽  
Author(s):  
Kerstin Skibbe ◽  
Ann-Kathrin Brethack ◽  
Annika Suenderhauf ◽  
Mohab Ragab ◽  
Annika Raschdorf ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Cells ◽  
Immune Cell ◽  
Aerobic Glycolysis ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Intestinal Barrier Function ◽  
High Amino Acid ◽  
Tumor Load

Background & Aims: To enable rapid proliferation, colorectal tumor cells up-regulate epidermal growth factor receptor (EGFR) signaling and perform high level of aerobic glycolysis, resulting in substantial lactate release into the tumor microenvironment and impaired anti-tumor immune responses. We hypothesized that an optimized nutritional intervention designed to reduce aerobic glycolysis of tumor cells may boost EGFR-directed antibody (Ab)-based therapy of pre-existing colitis-driven colorectal carcinoma (CRC). Methods: CRC development was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) administration to C57BL/6 mice. AOM/DSS treated mice were fed a glucose-free, high-protein diet (GFHPD) or an isoenergetic control diet (CD) in the presence or absence of i.p. injection of PBS, an irrelevant control mIgG2a or an anti-EGFR mIgG2a. Ex vivo, health status, tumor load, metabolism, colonic epithelial cell differentiation and immune cell infiltration were studied. Functional validation was performed in murine and human CRC cell lines MC-38 or HT29-MTX. Results: AOM/DSS treated mice on GFHPD displayed reduced systemic glycolysis, resulting in improved tumoral energy homeostasis and diminished tumor load. Comparable but not additive to an anti-EGFR-Ab therapy, GFHPD was accompanied by enhanced tumoral differentiation and decreased colonic PD-L1 and splenic PD-1 immune checkpoint expression, presumably promoting intestinal barrier function and improved anti-tumor immune responses. In vitro, glucose-free, high-amino acid culture conditions reduced proliferation but improved differentiation of CRC cells in combination with down-regulation of PD-L1 expression. Conclusion: We here found GFHPD to metabolically reprogram colorectal tumors towards balanced OXPHOS, thereby improving anti-tumor T-cell responses and reducing CRC progression with a similar efficacy as EGFR-directed antibody therapy.

scholarly journals An isoenergetic high-protein, moderate-fat diet does not compromise strength and fatigue during resistance exercise in women

2008 ◽  
Vol 100 (2) ◽  
pp. 283-286 ◽  
Author(s):  
Konstantina Dipla ◽  
Maria Makri ◽  
Andreas Zafeiridis ◽  
Dimitrios Soulas ◽  
Sofia Tsalouhidou ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Lower Limb ◽  
High Intensity ◽  
Handgrip Strength ◽  
Control Diet ◽  
High Protein Diet ◽  
High Protein ◽  
Lower Limbs ◽  
Protein Diet ◽  
Isometric Handgrip

Resistance exercise is recommended to individuals following high-protein diets in order to augment changes in body composition. However, alterations in macronutrient composition may compromise physical performance. The present study investigated the effects of an isoenergetic high-protein diet on upper and lower limb strength and fatigue during high-intensity resistance exercise. Ten recreationally active women, aged 25–40 years, followed a control diet (55, 15 and 30 % of energy from carbohydrate, protein and fat, respectively) and a high-protein diet (respective values, 30, 40 and 30) for 7 d each in a random counterbalanced design. Each participant underwent strength testing of upper limb (isometric handgrip strength and endurance) and lower limb (four sets of sixteen maximal knee flexions and extensions on an isokinetic dynamometer) before and after applying each diet. Body weight, body fat and RER were significantly reduced following the high-protein diet (P < 0·05). No differences were found between diets in any of the strength performance parameters (handgrip strength, handgrip endurance, peak torque, total work and fatigue) or the responses of heart rate, systolic and diastolic arterial pressure, blood lactate and blood glucose to exercise. Women on a short-term isoenergetic high-protein, moderate-fat diet maintained muscular strength and endurance of upper and lower limbs during high-intensity resistance exercise without experiencing fatigue earlier compared with a control diet.

Effect of a high protein diet on worm recovery, growth and distribution of Echinostoma caproni in ICR mice

1997 ◽  
Vol 71 (4) ◽  
pp. 351-354 ◽  
Author(s):  
J.E. Sudati ◽  
F. Rivas ◽  
B. Fried
Keyword(s):  
Control Diet ◽  
High Protein Diet ◽  
Dry Weight ◽  
High Protein ◽  
Protein Diet ◽  
Echinostoma Caproni ◽  
Icr Mice ◽  
Parasite Relationship ◽  
Standard Laboratory Diet ◽  
Relationship Of

AbstractThe effects of a high protein diet on the host-parasite relationship of Echinostoma caproni in ICR mice were studied. The customized high protein diet (CHPD) contained 64% casein as a source of protein. The control diet consisted of a standard laboratory diet containing 23% casein as a source of protein. Mice were each fed 25 cysts of E. caproni by stomach tube and necropsied 2, 3, 4 and 5 weeks postinfection. The weight of mice on the CHPD did not differ significantly from mice on the control diet. Worm recoveries were also unaffected by the high protein diet. There was a significant decline in worm dry weight, body area and uterine egg counts in worms from mice on the CHPD compared with those on the control diet. Worms from hosts on the CHPD were located more posteriad in the gut than those recovered from mice on the control diet. Changes in the mouse diet adversely affected E. caproni maturation and growth, possibly by altering the immediate host mucosal environment and making it less conducive to worm development.

Plasma cholecystokinin and pancreatic growth during adaptation to dietary protein

1986 ◽  
Vol 251 (1) ◽  
pp. G70-G74 ◽  
Author(s):  
G. M. Green ◽  
V. H. Levan ◽  
R. A. Liddle
Keyword(s):  
Food Intake ◽  
Control Diet ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Pancreatic Acini ◽  
Pancreatic Growth ◽  
Low Protein ◽  
Plasma Cholecystokinin ◽  
Pancreatic Protease

The relationship among plasma cholecystokinin (CCK), pancreatic growth, and food intake was studied in rats over a 2-wk period of adaptation from a very low-protein to a very high-protein diet. Rats adapted to a control diet (5% casein) were killed at 0900 (without fasting) at 0 h, 12 h, 24 h, 48 h, 7 days, or 14 days after transfer to a high-protein diet (75% casein). CCK was measured by bioassay using isolated pancreatic acini. Plasma CCK in high protein-fed rats was increased approximately threefold in the first 24 h, but returned to control (approximately 2.5 pM) values by day 7. Pancreatic weight, DNA, protein, and chymotrypsin(ogen) significantly increased to maximal values by day 7 in high protein-fed rats. Food intake in high protein-fed rats was inhibited by 47% after 24 h but returned to control values by day 7. The results indicate that high-protein diets initially increase CCK release and increase pancreatic protease secretory capacity and that, when pancreatic protease secretion is sufficient to match protein digestive requirements, the stimulus for CCK secretion is reduced and plasma CCK returns to normal. The pronounced but transient inhibition of food intake in high protein-fed rats is consistent with a role for CCK in regulation of food intake.

scholarly journals P007 GC1qR driven oxidative phosphorylation is essential for intestinal goblet cell differentiation

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S133-S133
Author(s):  
A SÜNDERHAUF ◽  
M Hicken ◽  
K Skibbe ◽  
H Schlichting ◽  
M Hirose ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Oxidative Phosphorylation ◽  
Goblet Cell ◽  
Intestinal Inflammation ◽  
Control Diet ◽  
Nutritional Intervention ◽  
Mucosal Inflammation ◽  
Mucosal Cell ◽  
Metabolic Switch ◽  
Goblet Cell Differentiation

Abstract Background Induction of goblet cell differentiation during inflammation has been shown to be impaired in ulcerative colitis (UC) but not Crohn’s disease (CD), possibly explaining the intestinal goblet cell and mucus reduction observed in active UC. A metabolic switch from glycolysis to mitochondrial oxidative phosphorylation (OXPHOS) is necessary for terminal differentiation of intestinal stem cells towards goblet cells. Interestingly, intestinal energy deficiency in general and reduced level of OXPHOS in specific have been attributed to UC pathogenesis more than 30 years ago. The c1q binding protein (C1QBP; gC1qR) is indispensable for the maintenance of OXPHOS. Nevertheless, experimental evidence linking mitochondrial dysfunction with goblet cell depletion and C1QBP expression are still missing. Methods Goblet cell differentiation was studied in human biopsies from UC patients in remission, in mucus-producing HT29MTX cells and in a conplastic mouse strain with diminished mitochondrial OXPHOS activity. Furthermore, mice were fed an experimental diet to shift cellular energy production from glycolysis to OXPHOS and mucosal cell differentiation was compared with mice on an isocaloric control diet. Results In vitro, siRNA experiments in HT29MTX cells showed that butyrate-induced expression of goblet cell differentiation factor KLF4 is highly dependent on gC1qR expression. Interestingly, the latter was significantly reduced in human ileal and colonic sections of UC patients in remission compared with HN. OXPHOS-deficient conplastic B6-mt FVB mice further confirmed these findings by depicting diminished klf4 expression, lowered goblet cell numbers, a thinned intestinal mucus layer and signs of intestinal inflammation. Finally, via nutritional intervention in C57BL/6 mice we were able to increase gC1qR level and to induce goblet cell differentiation via hath1 and klf4 compared with controls. Conclusion Taken together, we here describe a new pathway linking low intestinal expression of OXPHOS-regulating gC1qR to impaired goblet cell differentiation, mucus reduction and mucosal inflammation, which could be possibly reversed by nutritional intervention.

Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways

2009 ◽  
Vol 297 (1) ◽  
pp. E76-E84 ◽  
Author(s):  
Takashi Uebanso ◽  
Yutaka Taketani ◽  
Makiko Fukaya ◽  
Kazusa Sato ◽  
Yuichiro Takei ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Fatty Liver ◽  
Control Diet ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Fibroblast Growth Factor 21 ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Obese Rats

The mechanism by which replacement of some dietary carbohydrates with protein during weight loss favors lipid metabolism remains obscure. In this study, we investigated the effect of an energy-restricted, high-protein/low-carbohydrate diet on lipid metabolism in obese rats. High-sucrose-induced obese rats were assigned randomly to one of two energy-restricted dietary interventions: a carbohydrate-based control diet (CD) or a high-protein diet (HPD). Lean rats of the same age were assigned as normal control. There was significantly greater improvement in fatty liver and hypertriglyceridemia with the HPD diet relative to the CD diet. Expression of genes regulated by fibroblast growth factor-21 (FGF21) and involved in liver lipolysis and lipid utilitization, such as lipase and acyl-CoA oxidase, increased in obese rats fed the HPD. Furthermore, there was an inverse correlation between levels of FGF21 gene expression (regulated by glucagon/insulin balance) and increased triglyceride concentrations in liver from obese rats. Expression of hepatic stearoyl-CoA desaturase-1 (SCD1), regulated primarily by the dietary carbohydrate, was also markedly reduced in the HPD group (similar to plasma triglyceride levels in fasting animals) relative to the CD group. In conclusion, a hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia effectively relative to a carbohydrate diet. The two cellular pathways at work behind these benefits include stimulation of hepatic lipolysis and lipid utilization mediated by FGF21 and reduction of hepatic VLDL-TG production by SCD1 regulation.

scholarly journals FORMULATION AND NUTRITIONAL EVALUATION OF HIGH PROTEIN DIET PRODUCED FROM YELLOW MAIZE (Zea mays) SOYA BEAN (GLYCINE MAX), PUMPKIN (Cucurbita pepo) SEED AND FISH (Alestes nurse) MEAL

2021 ◽  
Vol 2 (2) ◽  
pp. 36-65
Author(s):  
G. Chamba ◽  
A. S. Falmata ◽  
B. P. Bintu ◽  
B. K. Maryam ◽  
S. Modu
Keyword(s):  
Amino Acid ◽  
Fish Meal ◽  
Control Diet ◽  
High Protein Diet ◽  
Amino Acid Profile ◽  
Soya Bean ◽  
High Protein ◽  
Protein Diet ◽  
Pumpkin Seed ◽  
Dried Fish

  The aim of this study was to produce high protein diet for growing children from yellow maize, soya bean, pumpkin seed and fish meal. The raw materials were subjected to different processing techniques. The yellow maize (YM) was blended with different proportions of soya bean (SB), pumpkin seeds (PS) and fish meal (FM) with a view to formulating a high protein diet to address protein Energy Malnutrition. The formulated food Blends were; Blend 1 (70 % YM: 30 % SB), Blend 2 (70 % YM: 30 % PS), Blend 3 (70 % YM: 30 % FM), Blend 4 (70 % YM: 20 % SB :10 % PS), Blend 5 (70 % YM: 15 % SB: 15 % FM), Blend 6 (60 % YM: 20 % PS: 20 % FM), and a therapeutic milk (F-100) was used as a control diet. The raw materials and the food Blends were assayed for proximate, mineral, vitamin content and amino acid profile. The data obtained were analyzed statistically. The results of the proximate composition showed significant (p<0.05) decrease in moisture, protein, total fat and fibre contents of the fermented yellow maize, roasted soya bean and pumpkin seed while that of the dried fish showed significant (P<0.05) increase.  The results shows that food Blend 6 had highest values for protein (17.77±0.09 %), total fat (6.00±0.27%) and total energy (388.10±0.29 Kcal/100g). A Significant (P<0.05) difference was observed in the mineral element content of yellow maize and fish meal after fermentation and drying respectively, while an increase was observed in roasted soya bean and pumpkin seed. The food Blend 5 recorded higher value for Na, and K, while the control diet had higher value for P, Zn, Fe and Cu. An increase in B-group vitamins, and vitamin C, were observed in the samples, while decreased in fat soluble vitamins A and E were observed in fermented yellow maize and dried fish, while decrease was observed in roasted soybean and pumpkin seed. The control diet had higher value for all the vitamins analyzed compared to the food Blends, except for vitamin A and E. The result of the amino acid profile showed that the levels of the essential amino acids were increased in the fermented yellow maize, and dried fish, while a reduction was observed in roasted soya bean and pumpkin seed. However, all the prepared food Blends were enhanced in terms of essential amino acid, but more enhanced in food Blend 6, followed very closely by food Blend 5. The amino acid profile of the control Blend was higher than those of the food Blends1, 2, 3 and 4. Thus, the high energy and protein contents of the formulated diets are adequate in the management of PEM.

Increased Myostatin Synthesis in Rat Gastrocnemius Muscles under High-Protein Diet

2006 ◽  
Vol 16 (2) ◽  
pp. 153-165 ◽  
Author(s):  
Koichi Nakazato ◽  
Tatsuro Hirose ◽  
Hongsun Song
Keyword(s):  
Muscle Hypertrophy ◽  
Gastrocnemius Muscle ◽  
Control Diet ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Protein Levels ◽  
Male Wistar Rats ◽  
Experimental Feeding ◽  
Gastrocnemius Muscles

More than 15% dietary protein has reportedly not led to significant muscle hypertrophy in normal growing rats. The aim of this study was to test whether a high protein (HP) diet affects myostatin (Mstn) synthesis in a rat gastrocnemius muscle. Twenty-four male Wistar rats (4-wk-old) were divided into three groups: 1) control diet (15% protein; 15P, n = 8), 2) the 25P group (25% protein, n = 8), and 3) the 35P group (35% protein, n = 8). After 3 wk of isoenergetic feedings, the Mstn level in skeletal muscles was determined using Northern and Western blotting analysis. After the experimental feeding, muscle masses were similar among groups. The 35P showed significant high expressions of Mstn both at mRNA and protein levels. Obtained results suggest that a high-protein diet leads to the high Mstn level to restrict muscle hypertrophy.

Food and protein intake, glucagon, and distribution of alpha-aminoisobutyrate in the rat

1980 ◽  
Vol 238 (4) ◽  
pp. E358-E363
Author(s):  
J. K. Tews ◽  
A. E. Harper
Keyword(s):  
Dietary Protein ◽  
Protein Intake ◽  
Control Diet ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Tissue Water ◽  
Low Protein ◽  
Protein Diets ◽  
Different Tissues

Distribution of alpha-aminoisobutyric acid (AIB) in the rat was modified by food, dietary protein, and glucagon. In rats last fed 24 h before AIB injection, AIB clearance from plasma and uptake into liver were greater in rats fed a high-protein diet (60% casein) than in rats fed the control diet (18% casein); AIB clearance from plasma and uptake into muscle were lowered by a low-protein diet (6% casein). Feeding rats lowered clearance of AIB from plasma in low- and high-protein groups. Distribution ratios (AIB concentration in tissue water/AIB in plasma) were low in all tissues but liver during the first 7 h after feeding high protein when compared to the control values; ratios were low in muscle, heart, and kidney after feeding low protein. Maximum ratios occurred at different times for different tissues; the time was delayed by the high-protein diet in all tissues but liver. Glucagon increased all ratios in rats fed the control or low-protein diets, with the smallest changes occurring in liver and muscle from low-protein rats.

Luminal dietary protein, not amino acids, induces pancreatic protease via CCK in pancreaticobiliary-diverted rats

2000 ◽  
Vol 278 (6) ◽  
pp. G937-G945 ◽  
Author(s):  
Hiroshi Hara ◽  
Sumika Ohyama ◽  
Tohru Hira
Keyword(s):  
Amino Acids ◽  
Direct Action ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Intestinal Lumen ◽  
Casein Diet ◽  
Acid Diet ◽  
High Amino Acid ◽  
Pancreatic Proteases

We determined whether pancreatic adaptation to a high-protein diet depends on ingested protein in the intestinal lumen and whether such adaptation depends on a CCK or capsaicin-sensitive vagal afferent pathway in pancreaticobiliary-diverted (PBD) rats. Feeding a high-casein (60%) diet but not a high-amino acid diet to PBD rats increased pancreatic trypsin and chymotrypsin activities compared with those after feeding a 25% casein diet. In contrast, feeding both the high-nitrogen diets induced pancreatic hypertrophy in PBD rats. These pancreatic changes by the diets were abolished by treatment with devazepide, a CCK-A receptor antagonist. Protease zymogen mRNA abundance in the PBD rat was not increased by feeding the high-casein diet and was decreased by devazepide. Perivagal capsaicin treatment did not influence the values of any pancreatic variables in PBD rats fed the normal or high-casein diet. We concluded that luminal protein or peptides were responsible for the bile pancreatic juice-independent induction of pancreatic proteases on feeding a high-protein diet. The induction was found to be dependent on the direct action of CCK on the pancreas. Pancreatic growth induced by high-protein feeding in PBD rats may depend at least partly on absorbed amino acids.

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