Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice

Although the association between maternal periconceptional diet and adult offspring health is well characterised, our understanding of the impact of paternal nutrition at the time of conception on offspring phenotype remains poorly defined. Therefore, we determined the effect of a paternal preconception low protein diet (LPD on adult offspring cardiovascular and metabolic health in mice. Male C57BL/6 mice were fed either normal protein diet (NPD; 18% casein or LPD (9% casein for 7 wk before mating. At birth, a reduced male-to-female ratio (P = 0.03 and increased male offspring weight (P = 0.009 were observed in litters from LPD compared with NPD stud males with no differences in mean litter size. LPD offspring were heavier than NPD offspring at 2 and 3 wk of age (P <0.02. However, no subsequent differences in body weight were observed. Adult male offspring derived from LPD studs developed relative hypotension (decreased by 9.2 mmHg and elevated heart rate (P <0.05, whereas both male and female offspring displayed vascular dysfunction and impaired glucose tolerance relative to NPD offspring. At cull (24 wk, LPD males had elevated adiposity (P = 0.04, reduced heart-to-body weight ratio (P = 0.04, and elevated circulating TNF-α levels (P = 0.015 compared with NPD males. Transcript expression in offspring heart and liver tissue was reduced for genes involved in calcium signaling (Adcy, Plcb, Prkcb and metabolism (Fto in LPD offspring (P <0.03. These novel data reveal the impact of suboptimal paternal nutrition on adult offspring cardiovascular and metabolic homeostasis, and provide some insight into the underlying regulatory mechanisms.

Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health

Previously, we have shown that a maternal low protein diet, fed exclusively during the preimplantation period of mouse development (Emb-LPD), is sufficient to induce by the blastocyst stage a compensatory growth phenotype in late gestation and postnatally, correlating with increased risk of adult onset cardiovascular disease and behavioural dysfunction. Here, we examine mechanisms of induction of maternal Emb-LPD programming and early compensatory responses by the embryo. Emb-LPD induced changes in maternal serum metabolites at the time of blastocyst formation (E3.5), notably reduced insulin and increased glucose, together with reduced levels of free amino acids (AAs) including branched chain AAs leucine, isoleucine and valine. Emb-LPD also caused reduction in the branched chain AAs within uterine fluid at the blastocyst stage. These maternal changes coincided with an altered content of blastocyst AAs and reduced mTORC1 signalling within blastocysts evident in reduced phosphorylation of effector S6 ribosomal protein and its ratio to total S6 protein but no change in effector 4E-BP1 phosphorylated and total pools. These changes were accompanied by increased proliferation of blastocyst trophectoderm and total cells and subsequent increased spreading of trophoblast cells in blastocyst outgrowths. We propose that induction of metabolic programming following Emb-LPD is achieved through mTORC1signalling which acts as a sensor for preimplantation embryos to detect maternal nutrient levels via branched chain AAs and/or insulin availability. Moreover, this induction step associates with changes in extra-embryonic trophectoderm behaviour occurring as early compensatory responses leading to later nutrient recovery. © 2012 Fleming et al.

Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age

Human and animal studies have revealed a strong association between periconceptional environmental factors, such as poor maternal diet, and an increased propensity for cardiovascular and metabolic disease in adult offspring. Previously, we reported cardiovascular and physiological effects of maternal low protein diet (LPD) fed during discrete periods of periconceptional development on 6-month-old mouse offspring. Here, we extend the analysis in 1 year aging offspring, evaluating mechanisms regulating growth and adiposity. Isocaloric LPD (9% casein) or normal protein diet (18% casein; NPD) was fed to female MF-1 mice either exclusively during oocyte maturation (for 3.5 days prior to mating; Egg-LPD, Egg-NPD, respectively), throughout gestation (LPD, NPD) or exclusively during preimplantation development (for 3.5 days post mating; Emb-LPD). LPD and Emb-LPD female offspring were significantly lighter and heavier than NPD females respectively for up to 52 weeks. Egg-LPD, LPD and Emb-LPD offspring displayed significantly elevated systolic blood pressure at 52 weeks compared to respective controls (Egg-NPD, NPD). LPD females had significantly reduced inguinal and retroperitoneal fat pad: body weight ratios compared to NPD females. Expression of the insulin receptor (Insr) and insulin-like growth factor I receptor (Igf1r) in retroperitoneal fat was significantly elevated in Emb-LPD females (P&0.05), whilst Emb-LPD males displayed significantly decreased expression of the mitochondrial uncoupling protein 1 (Ucp1) gene compared to NPD offspring. LPD females displayed significantly increased expression of Ucp1 in interscapular brown adipose tissue when compared to NPD offspring. Our results demonstrate that aging offspring body weight, cardiovascular and adiposity homeostasis can be programmed by maternal periconceptional nutrition. These adverse outcomes further exemplify the criticality of dietary behaviour around the time of conception on long-term offspring health. © 2011 Watkins et al.

Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring

Environmental perturbations during early mammalian development can affect aspects of offspring growth and cardiovascular health. We have demonstrated previously that maternal gestational dietary protein restriction in mice significantly elevated adult offspring systolic blood pressure. Therefore, the present study investigates the key mechanisms of blood pressure regulation in these mice. Following mating, female MF-1 mice were assigned to either a normal-protein diet (NPD; 18% casein) or an isocaloric low-protein diet throughout gestation (LPD; 9% casein), or fed the LPD exclusively during the pre-implantation period (3.5d) before returning to the NPD for the remainder of gestation (Emb-LPD). All offspring received standard chow. At 22 weeks, isolated mesenteric arteries from LPD and Emb-LPD males displayed significantly attenuated vasodilatation to isoprenaline (P=0.04 and P=0.025, respectively), when compared with NPD arteries. At 28 weeks, stereological analysis of glomerular number in female left kidneys revealed no significant difference between the groups. Real-time RT-PCR analysis of type 1a angiotensin II receptor, Na /K ATPase transporter subunits and glucocorticoid receptor expression in male and female left kidneys revealed no significant differences between the groups. LPD females displayed elevated serum angiotensin-converting enzyme (ACE) activity (P=0.044), whilst Emb-LPD males had elevated lung ACE activity (P=0.001), when compared with NPD offspring. These data demonstrate that elevated offspring systolic blood pressure following maternal gestational protein undernutrition is associated with impaired arterial vasodilatation in male offspring, elevated serum and lung ACE activity in female and male offspring, respectively, but kidney glomerular number in females and kidney gene expression in male and female offspring appear unaffected. © 2010 The Authors.

Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring

Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P <0.05). Maternal LPD offspring also exhibited elevated systolic blood pressure (SBP) in males at 9 and 15 weeks and in both sexes at 21 weeks (P <0.05). Male LPD offspring hypertension was accompanied by attenuated arterial responsiveness in vitro to vasodilators acetylcholine and isoprenaline (P <0.05). LPD female offspring adult kidneys were also smaller, but had increased nephron numbers (P <0.05). Moreover, the relationship between SBP and kidney or heart size or nephron number was altered by diet treatment (P <0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome. © Journal compilation © 2008 The Physiological Society.

The Maintenance and Consequences of a Low Quality Diet in Poecilia Latipinna

The adaptive significance of herbivory in nature is not well understood. In order to document the conditions that select for an herbivorous feeding habit, we must first understand how such a diet is maintained, and the consequences of doing so. A few studies have begun to reveal mechanisms of maintaining herbivory (i.e. selective feeding, diet mixing, etc.) and the associated life history responses (i.e. growth, reproduction, etc.) in terrestrial and marine systems; however, studies of this kind are underrepresented in the freshwater literature. In this study, I use the sailfin molly (Poecilia latipinna) as a model organism to examine diet selectivity and the effects of an herbivorous diet on growth. To study food selectivity, sailfin mollies were fed either disturbed or intact periphyton mats from one of three localities within the Everglades (Water Conservation Area 3B, the Gap, or Chekika). Mats are structured with palatable algal species (i.e. greens and diatoms) comprising the inner components of the mat, and unpalatable species (i.e. cyanobacteria) comprising the outer edges. Fish gut contents were analyzed for each treatment and periphyton locality. Results suggest that when provided access to the inner components of the mats, fish preferentially eat more palatable algae. In a second experiment, effects of an herbivorous diet were examined using neonate sailfin mollies. Fish were fed either commercial food flakes, commercial algae flakes, or ground periphyton, and growth rate was measured weekly, from birth to 21 days. Fish fed the commercial diets grew at a faster rate and reached a larger final size than those fed periphyton. These results suggest that a periphyton diet is limited in nutritional elements compared to a pure algae diet and herbivorous organisms feeding upon it may experience negative effects on growth. By studying the costs and benefits of herbivory in a freshwater system, this paper contributes to a larger study of the question of why herbivory would evolve as an adaptation when seemingly inefficient compared to carnivorous and omnivorous diets.

The functional and clinical outcomes of exercise training following a very low energy diet for severely obese women: study protocol for a randomised controlled trial

BACKGROUND: Clinical practice guidelines globally recommend lifestyle modification including diet and exercise training as first-line treatment for obesity. The clinical benefits of exercise training in adults with obesity is well-documented; however, there is no strong evidence for the effectiveness of exercise training for weight loss in class II and class III obesity. The purpose of the randomised controlled trial described in this protocol article is to examine the effect of exercise training, in addition to a very low energy diet (VLED), in clinically severe obese women for changes in body composition, physical function, quality of life, and markers of cardiometabolic risk.

METHODS/DESIGN: Sixty women, aged 18-50 years with a body mass index (BMI) greater than 34.9 kg.m(2) and at least one obesity-related co-morbidity, will be recruited for this 12-month study. Participants will be randomised to either exercise plus energy restriction (n = 30), or energy restriction alone (n = 30). All participants will follow an energy-restricted individualised diet incorporating a VLED component. The exercise intervention group will also receive exercise by supervised aerobic and resistance training and a home-based exercise programme totalling 300 minutes per week. Primary outcome measures include body composition and aerobic fitness. Secondary outcome measures include: physical function, cardiometabolic risk factors, quality of life, physical activity, and mental health. All outcome measures will be conducted at baseline, 3, 6 and 12 months.

DISCUSSION: Previous research demonstrates various health benefits of including exercise training as part of a healthy lifestyle at all BMI ranges. Although clinical practice guidelines recommend exercise training as part of first-line treatment for overweight and obesity, there are few studies that demonstrate the effectiveness of exercise in class II and class III obesity. The study aims to determine whether the addition of exercise training to a VLED provides more favourable improvements in body composition, physical function, quality of life, and markers of cardiometabolic risk for women with clinically severe obesity, compared to VLED alone.

Dietary protein restriction as a treatment for slowing chronic kidney disease progression: The case against

Low-protein diets (

Effect of a low sodium DASH diet, including red meat on blood pressure in post-menopausal women

Background – The DASH type dietary pattern which consists of high fruit, vegetable and dairy products and low saturated fat, is “base-producing” but restricts red meat with no clear justification.
Objective – To compare the BP-lowering effect of Vitality diet (VD), a moderately low sodium, “base” producing modified DASH diet, containing 6 serves/week of lean red meat to a “ high carbohydrate, low fat diet (HCLF diet), with a higher dietary acid load in post-menopausal women.
Design – Ninety-five hypertensive post-menopausal women (46 VD and 49 HCLF) completed a 14-wk randomised parallel study. Home BP was measured daily. Repeat 24-h dietary records and 24-h urine samples were collected fortnightly. Dietary acid load, expressed as potential renal acid load (PRAL), was calculated from nutrient intakes.
Outcomes – During the intervention, the VD group had an average daily consumption of 85 g cooked red meat. They had a mean (± SEM) reduction of 38 ± 7 mmol/d in urinary sodium excretion (P <0.0001), and a 7 ± 4 mmol/d increase in urinary potassium (P = 0.0681), with an estimated 23.1± 2.3 mEq/d lower PRAL than the HCLF group (P <0.0001). The fall in systolic pressure in the VD group tended to be greater by 3 ± 2 mmHg (P = 0.08) than the fall in systolic pressure seen with the HCLF diet. A greater BP-lowering effect of VD was observed among those taking anti-hypertensive medication (n = 17) with a greater 5.5 ± 2.7 mm Hg (P = 0.0518) reduction of systolic BP and greater reduction in diastolic BP by 3.6 ± 1.7 mm Hg (P = 0.0388) compared to the HCLF diet. However, no relationship between BP and PRAL was observed.
Conclusions – A low sodium DASH type dietary pattern with the inclusion of lean red meat was effective in reducing BP in post-menopausal women, particularly in those taking anti-hypertensive medication. This dietary pattern could be recommended for this group who are at increased risk of cardiovascular disease.
This study was funded by Meat & Livestock Australia.

Diet high in monounsaturated fat does not have a different effect on arterial elasticity than a low-fat, high-carbohydrate diet

Objective : To compare the effects of a modified-fat diet high in monounsaturated fat, and a low-fat/high-carbohydrate diet on arterial elasticity.
Design : Randomized crossover design; each diet period was 1 month and a 2-week wash out period occurred in between.
Subjects/setting : Thirty healthy, free-living, nonsmoking men and women were recruited from the Melbourne, Australia, metropolitan region of Australia. Men were aged 35 to 55 years and postmenopausal women were aged 50 to 60 years and were not taking hormone replacement therapy. Twenty-eight subjects completed the study.
Intervention : Two diets of equal energy value: a modified-fat diet and a low-fat/high-carbohydrate diet; the modified-fat diet had 3 times more energy from monounsaturated fat.
Main outcome measures : Arterial elasticity and serum lipoprotein concentrations.
Statistical analysis : The general linear model was used to investigate overall effect and any carryover or order effects. Paired t test and the general linear model were used to compare the results from the 2 diet periods.
Results : High-density lipoprotein cholesterol concentration was significantly higher on the modified-fat diet than on the low-fat/low-carbohydrate diet. Arterial elasticity and concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were not significantly different on the 2 diets.
Applications/conclusions : There is no evidence to favor a diet high in monounsaturated fat over a low-fat/high-carbohydrate diet because of an effect on arterial elasticity. Other changes in diet may be needed to cause a beneficial effect on arterial elasticity.

Consumption of a low glycaemic index diet in late life extends lifespan of Balb/c mice with differential effects on DNA damage

Background : Caloric restriction is known to extend the lifespan of all organisms in which it has been tested. Consequently, current research is investigating the role of various foods to improve health and lifespan. The role of various diets has received less attention however, and in some cases may have more capacity to improve health and longevity than specific foods alone. We examined the benefits to longevity of a low glycaemic index (GI) diet in aged Balb/c mice and examined markers of oxidative stress and subsequent effects on telomere dynamics.

Results : In an aged population of mice, a low GI diet extended average lifespan by 12%, improved glucose tolerance and had impressive effects on amelioration of oxidative damage to DNA in white blood cells. Telomere length in quadriceps muscle showed no improvement in the dieted group, nor was telomerase reactivated.

Conclusion : The beneficial effects of a low GI diet are evident from the current study and although the impact to telomere dynamics late in life is minimal, we expect that earlier intervention with a low GI diet would provide significant improvement in health and longevity with associated effects to telomere homeostasis.

Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet

 Hepatic insulin resistance is a major risk factor for the development of type 2 diabetes and is associated with the accumulation of lipids, including diacylglycerol (DAG), triacylglycerols (TAG) and ceramide. There is evidence that enzymes involved in ceramide or sphingolipid metabolism may have a role in regulating concentrations of glycerolipids such as DAG and TAG. Here we have investigated the role of sphingosine kinase (SphK) in regulating hepatic lipid levels. We show that mice on a high-fat high-sucrose diet (HFHS) displayed glucose intolerance, elevated liver TAG and DAG, and a reduction in total hepatic SphK activity. Reduced SphK activity correlated with downregulation of SphK1, but not SphK2 expression, and was not associated with altered ceramide levels. The role of SphK1 was further investigated by overexpressing this isoform in the liver of mice in vivo. On a low-fat diet (LFD) mice overexpressing liver SphK1, displayed reduced hepatic TAG synthesis and total TAG levels, but with no change to DAG or ceramide. These mice also exhibited no change in gluconeogenesis, glycogenolysis or glucose tolerance. Similarly, overexpression of SphK1 had no effect on the pattern of endogenous glucose production determined during a glucose tolerance test. Under HFHS conditions, normalization of liver SphK activity to levels observed in LFD controls did not alter hepatic TAG concentrations. Furthermore, DAG, ceramide and glucose tolerance were also unaffected. In conclusion, our data suggest that SphK1 plays an important role in regulating TAG metabolism under LFD conditions.

Effects of low fat and babassu fat diets on nutritional status in obstructive cholestasis in young rats

OBJETIVO: Testar os efeitos de uma dieta com baixo teor de gordura comparada a uma dieta com gordura de babaçu sobre o estado nutricional em ratos jovens com colestase obstrutiva. MÉTODOS: Submetemos 40 ratos divididos em quatro grupos de 10 animais a partir do P21 (21º dia pós-natal) até o P49 a dois dos seguintes tratamentos: ligadura e ressecção do ducto biliar comum ou operação simulada e dieta com baixo teor de gordura (óleo de milho fornecendo 4,5% da quantidade total de calorias) ou dieta com gordura de babaçu (essa gordura fornecendo 32,7% e óleo de milho fornecendo 1,7% da quantidade total de calorias). Foi mensurado o ganho de peso a cada 4 dias do P25 ao P49. A função de crescimento de Verhulst foi ajustada aos valores de ganho de peso. A velocidade e a aceleração de crescimento nos mesmos momentos foram estimadas usando a mesma equação. Foram mensurados: quantidade de ração ingerida e ingestão energética total do P21 ao P49, utilização de energia do P25 ao P49, gordura absorvida e balanço de nitrogênio (BN) do P42 ao P49. A ANOVA com dois fatores e o método de S.N.K para comparações pareadas foram utilizados para estudar os efeitos, sobre as variáveis, da colestase e das dietas e sua interação (p<0,05). RESULTADOS: em ratos com colestase e dieta com baixo teor de gordura, houve maior velocidade de crescimento no P45, maior aceleração de crescimento no P41 e P45, maior utilização de energia, maior percentual de gordura absorvida e maior BN do que em ratos com colestase e dieta com gordura de babaçu. CONCLUSÃO: A dieta com baixo teor de gordura atenua a restrição de crescimento provocada pela colestase e proporciona melhor aproveitamento da dieta e maior incorporação da proteína ingerida do que a dieta com gordura de babaçu.

Effects of swim training on liver carcinogenesis in male Wistar rats fed a low-fat or high-fat diet

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)