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A low carbohydrate, high protein diet combined with celecoxib markedly reduces metastasis.

ABSTRACT: We recently demonstrated that both murine and human carcinomas grow significantly slower in mice on low carbohydrate (CHO), high protein diets than on isocaloric Western diets and that a further reduction in tumor growth rates occur when the low CHO diets are combined with the cyclooxygenase-2 inhibitor, celecoxib. Following upon these studies, we asked herein what effect low CHO, high protein diets, with or without celecoxib, might have on tumor metastasis. In the highly metastatic 4T1 mouse mammary tumor model, a 15% CHO, high protein diet supplemented with celecoxib (1 g/kg chow) markedly reduced lung metastases. Moreover, in longer-term studies using male Transgenic Adenocarcinoma of the Mouse Prostate mice, which are predisposed to metastatic prostate cancer, the 15% CHO diet, with and without celecoxib (0.3 g/kg chow), gave the lowest incidence of metastases, but a more moderate 25% CHO diet containing celecoxib led to the best survival. Metabolic studies with 4T1 tumors suggested that the low CHO, high protein diets may be forcing tumors to become dependent on amino acid catabolism for survival/growth. Taken together, our results suggest that a combination of a low CHO, high protein diet with celecoxib substantially reduces metastasis.

SUBMITTER: Ho VW

PROVIDER: S-EPMC4178469 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Low-protein/high carbohydrate diet

Project description:Low-protein/high carbohydrate (LP/HC) diet promotes metabolic health and longevity in adult human and animal models. However, the complex molecular underpinnings of how LP/HC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LP/HC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous adipose tissue (sWAT). In particular, we measured Ucp1 induction in association with up-regulation of actomyosin components and several Serca (Serca1, Serca2a, Serca2b) ATPases. In beige adipocytes, we observed that AMPK activation is responsible for transducing the amino acid lowering in an enhanced fat catabolism, which sustains both Ucp1- and Serca-dependent energy dissipation. Limiting AMPK activation counteracts the expression of brown fat and muscular genes, including Ucp1 and Serca, as well as mitochondrial oxidative genes. We observed that mitochondrial reactive oxygen species are the upstream molecules controlling AMPK-mediated metabolic rewiring in amino acid-restricted beige adipocytes. Our findings delineate a novel metabolic phenotype of responses to amino acid shortage, which recapitulates some of the benefits of cool temperature in sWAT. In conclusion, this study highlights LP/HC diet as a valuable and practicable strategy to prevent metabolic diseases through the enhancement of mitochondrial oxidative metabolism and the recruitment of different energy dissipating routes in beige adipocytes.

2021-09-09 | PXD017786 | Pride

Vascular effects of a low-carbohydrate high-protein diet.

Project description:The cardiovascular complications of obesity have prompted interest in dietary interventions to reduce weight, including low-carbohydrate diets that are generally high in protein and fat. However, little is known about the long-term effects of these diets on vascular health. We examined the cardiovascular effects of a low-carbohydrate, high-protein diet (LCHP) in the ApoE(-/-) mouse model of atherosclerosis and in a model of ischemia-induced neovascularization. Mice on a LCHP were compared with mice maintained on either the standard chow diet (SC) or the Western diet (WD) which contains comparable fat and cholesterol to the LCHP. LCHP-fed mice developed more aortic atherosclerosis and had an impaired ability to generate new vessels in response to tissue ischemia. These changes were not explained by alterations in serum cholesterol, inflammatory mediators or infiltrates, or oxidative stress. The LCHP diet substantially reduced the number of bone marrow and peripheral blood endothelial progenitor cells (EPCs), a marker of vascular regenerative capacity. EPCs from mice on a LCHP diet also manifest lower levels of activated (phosphorylated) Akt, a serine-threonine kinase important in EPC mobilization, proliferation, and survival. Taken together, these data demonstrate that in animal models LCHP diets have adverse vascular effects not reflected in serum markers and that nonlipid macronutrients can modulate vascular progenitor cells and pathophysiology.

| S-EPMC2741266 | biostudies-literature

Effects of a plant-based high-carbohydrate/high-fiber diet versus high-monounsaturated fat/low-carbohydrate diet on postprandial lipids in type 2 diabetic patients.

Project description:OBJECTIVE:To search for a better dietary approach to treat postprandial lipid abnormalities and improve glucose control in type 2 diabetic patients. RESEARCH DESIGN AND METHODS:According to a randomized crossover design, 18 type 2 diabetic patients (aged 59 +/- 5 years; BMI 27 +/- 3 kg/m(2)) (means +/- SD) in satisfactory blood glucose control on diet or diet plus metformin followed a diet relatively rich in carbohydrates (52% total energy), rich in fiber (28 g/1,000 kcal), and with a low glycemic index (58%) (high-carbohydrate/high-fiber diet) or a diet relatively low in carbohydrate (45%) and rich in monounsaturated fat (23%) (low-carbohydrate/high-monounsaturated fat diet) for 4 weeks. Thereafter, they shifted to the other diet for 4 more weeks. At the end of each period, plasma glucose, insulin, lipids, and lipoprotein fractions (separated by discontinuous density gradient ultracentrifugation) were determined on blood samples taken at fasting and over 6 h after a test meal having a similar composition as the corresponding diet. RESULTS:In addition to a significant decrease in postprandial plasma glucose, insulin responses, and glycemic variability, the high-carbohydrate/high-fiber diet also significantly improved the primary end point, since it reduced the postprandial incremental areas under the curve (IAUCs) of triglyceride-rich lipoproteins, in particular, chylomicrons (cholesterol IAUC: 0.05 +/- 0.01 vs. 0.08 +/- 0.02 mmol/l per 6 h; triglycerides IAUC: 0.71 +/- 0.35 vs. 1.03 +/- 0.58 mmol/l per 6 h, P < 0.05). CONCLUSIONS:A diet rich in carbohydrate and fiber, essentially based on legumes, vegetables, fruits, and whole cereals, may be particularly useful for treating diabetic patients because of its multiple effects on different cardiovascular risk factors, including postprandial lipids abnormalities.

| S-EPMC2782970 | biostudies-literature

No adverse effect of a parental low protein/high carbohydrate diet on their offspring, in rainbow trout

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-16 | GSE169003 | GEO

Programming of the hepatic lipid metabolism via a parental high carbohydrate low protein diet in rainbow trout

Project description:In rainbow trout (Oncorhynchus mykiss), the effect of a paternal and a maternal high carbohydrate-low protein diet was assessed on progeny at long term. To this purpose, two-year old male and female rainbow trout were fed either a control diet or a high carbohydrate/low protein diet for an entire reproductive cycle for females and for 5 months for males. Crossed-fertilizations were carried out in order to obtain 4 groups of offspring. Offspring were fed with a commercial diet until they reached a market size and were then challenged with a complete plant-based diet for 3 months. After the challenge, hepatic transcriptomes were analysed to detect any effect of the parental diet on offspring metabolism.

2022-07-31 | GSE184632 | GEO

Gene expression analysis of subcutaneous adipose tissue in mice fed with a low-protein/high carbohydrate diet

Project description:In this experiment, we have analyzed the effects of a 2-weeks treatment with a low-protein/high carbohydrate diet (7P:70C) on subcutaneous adipose tissue of C57BL6/J male mice. Age and sex-matched mice fed with a Western diet (23P:57C) were used as controls.

2020-03-14 | E-MTAB-8850 | biostudies-arrayexpress

The potential of a high protein-low carbohydrate diet to preserve intrahepatic triglyceride content in healthy humans.

Project description:BackgroundProtein supplementation has been shown to reduce the increases in intrahepatic triglyceride (IHTG) content induced by acute hypercaloric high-fat and high-fructose diets in humans.ObjectiveTo assess the effect of a 12-wk iso-energetic high protein-low carbohydrate (HPLC) diet compared with an iso-energetic high carbohydrate-low protein (HCLP) diet on IHTG content in healthy non-obese subjects, at a constant body weight.DesignSeven men and nine women [mean ± SD age: 24 ± 5 y; BMI: 22.9 ± 2.1 kg/m2] were randomly allocated to a HPLC [30/35/35% of energy (En%) from protein/carbohydrate/fat] or a HCLP (5/60/35 En%) diet by stratification on sex, age and BMI. Dietary guidelines were prescribed based on individual daily energy requirements. IHTG content was measured by 1H-magnetic resonance spectroscopy before and after the dietary intervention.ResultsIHTG content changed in different directions with the HPLC (CH2H2O: 0.23 ± 0.17 to 0.20 ± 0.10; IHTG%: 0.25 ± 0.20% to 0.22 ± 0.11%) compared with the HCLP diet (CH2H2O: 0.34 ± 0.20 vs. 0.38 ± 0.21; IHTG%: 0.38 ± 0.22% vs. 0.43 ± 0.24%), which resulted in a lower IHTG content in the HPLC compared with the HCLP diet group after 12 weeks, which almost reached statistical significance (P = 0.055).ConclusionsA HPLC vs. a HCLP diet has the potential to preserve vs. enlarge IHTG content in healthy non-obese subjects at a constant body weight.Trial registrationClinicaltrials.gov NCT01551238.

| S-EPMC4199596 | biostudies-literature

Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenesis in subcutaneous adipose tissue.

Project description:Low-protein/high-carbohydrate (LPHC) diet has been suggested to promote metabolic health and longevity in adult humans and animal models. However, the complex molecular underpinnings of how LPHC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LPHC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous white adipose tissue (sWAT). In particular, we measured Ucp1 induction in association with up-regulation of actomyosin components and several Serca (Serca1, Serca2a, Serca2b) ATPases. In beige adipocytes, we observed that AMPK activation is responsible for transducing the amino acid lowering in an enhanced fat catabolism, which sustains both Ucp1-and Serca-dependent energy dissipation. Limiting AMPK activation counteracts the expression of brown fat and muscular genes, including Ucp1 and Serca, as well as mitochondrial oxidative genes. We observed that mitochondrial reactive oxygen species are the upstream molecules controlling AMPK-mediated metabolic rewiring in amino acid-restricted beige adipocytes. Our findings delineate a novel metabolic phenotype of responses to amino acid shortage, which recapitulates some of the benefits of cool temperature in sWAT. In conclusion, this highlights LPHC diet as a valuable and practicable strategy to prevent metabolic diseases through the enhancement of mitochondrial oxidative metabolism and the recruitment of different energy dissipating routes in beige adipocytes.

| S-EPMC7358542 | biostudies-literature

High carbohydrate-low protein consumption maximizes Drosophila lifespan.

Project description:Dietary restriction extends lifespan in a variety of organisms, but the key nutritional components driving this process and how they interact remain uncertain. In Drosophila, while a substantial body of research suggests that protein is the major dietary component affecting longevity, recent studies claim that carbohydrates also play a central role. To clarify how nutritional factors influence longevity, nutrient consumption and lifespan were measured on a series of diets with varying yeast and sugar content. We show that optimal lifespan requires both high carbohydrate and low protein consumption, but neither nutrient by itself entirely predicts lifespan. Increased dietary carbohydrate or protein concentration does not always result in reduced feeding-the regulation of food consumption is best described by a constant daily caloric intake target. Moreover, due to differences in food intake, increased concentration of a nutrient within the diet does not necessarily result in increased consumption of that particular nutrient. Our results shed light on the issue of dietary effects on lifespan and highlight the need for accurate measures of nutrient intake in dietary manipulation studies.

| S-EPMC3687007 | biostudies-literature

No adverse effect of a parental low protein/high carbohydrate diet on their offspring, in rainbow trout (muscle)

Project description:In rainbow trout (Oncorhynchus mykiss), the effect of a paternal and a maternal high carbohydrate-low protein diet was assessed on progeny at long term. To this purpose, two-year old male and female rainbow trout were fed either a control diet or a high carbohydrate/low protein diet for an entire reproductive cycle for females and for 5 months for males. Crossed-fertilizations were carried out in order to obtain 4 groups of offspring. Offspring were fed with a commercial diet until they reached a market size. At this stage, muscle transcriptomes were analysed to detect any effect of the parental diet on offspring metabolism.

2021-08-16 | GSE169002 | GEO

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