Modest Diet Research Articles

Murine HSD17β13 does not control liver steatosis and modestly impacts fibrosis in a sex- and diet-specific manner

Human genetic studies show that loss of function mutations in 17-Beta hydroxysteroid dehydrogenase (HSD17β13) are associated with protection from non-alcoholic steatohepatitis (NASH). As a result, therapies that reduce HSD17β13 are being pursued for the treatment of NASH. However, inconsistent effects on steatosis, inflammation, and fibrosis pathogenesis have been reported in murine Hsd17b13 knockdown or knockout models. To clarify whether murine Hsd17b13 loss regulates liver damage and fibrosis, we characterized Hsd17b13 knockout mice subjected to pro-NASH diets or pro-inflammatory chemical-induced liver injury. There were no effects of Hsd17b13 loss on liver injury, inflammation, fibrosis, or lipids after 28 weeks on the Gubra-Amylin NASH (GAN) diet or 12 weeks on a 45% choline-deficient high-fat diet (CDAHFD). However, AAV-mediated re-expression of murine Hsd17b13 in KO mice increased liver macrophage abundance in both sexes fed the 45% CDAHFD. In contrast, there was a modest reduction in liver fibrosis, but not lipids or inflammation within Hsd17b13 null female, but not male, mice after 12 weeks of a 60% CDAHFD compared to WT littermates. Fibrosis and the abundance of liver macrophages were increased in Hsd17b13 KO females upon adenoviral re-expression of mouse HSD17β13, but this was not reflected in inflammatory markers. Additionally, we found minimal differences in liver injury, lipids, or inflammatory and fibrotic markers 48 h after acute CCl4 exposure. In summary, murine Hsd17b13 loss has modest diet- and sex-specific effects on liver fibrosis which contrasts with human genetic studies. This suggests a disconnect between the biological function of HSD17β13 in mice and humans.

Differential depot-specific effects of long-term fructose intake on lipoprotein lipase activity and adipose tissue development in lean and obese+NIDDM SHR/Ntul//-cp rats

To determine the effects of a lower glycemic index, fructose-rich diet on parameters of weight gain and adipose tissue cellularity in principle fat depots, groups of congenic lean and obese+NIDDM SHR/tul//-cp rats were fed nutritionally complete isoenergetic diets where 54% of the calories were present as cooked cornstarch (CCS diet) or equal parts CCS and fructose (the CCSF diet) plus essential fats, proteins, minerals and dietary fibers from one until 9 months of age. Initial body weights were similar in all groups. Net weight gain and final body weights of obese >>>lean and demonstrated only a modest trend toward a greater weight gain in obese animals fed the CCSF diet. Differential effects on adipocyte size and number including marked hyperplasia and hypertrophy were observed in retroperitoneal and dorsal fat pads, while the mass and cellularity of the epididymal depots were similar in all dietary and phenotype groups. Tissue Lipoprotein Lipase activity (LPLA) was similar in EPI, RP, and Dorsal fat depots in both phenotypes, but LPLA in IBAT of lean >>> obese and demonstrated a modest diet effect (CSS > CSSF) in both phenotypes. These results indicate that the long-term consumption of the high fructose diet was neither substantially beneficial nor ameliorative in contributing to the modest excess weight gain and adiposity in WAT depots of the obese phenotype of this strain, despite the lower glycemic index and slower luminal digestibility of fructose vs cornstarch when fed in isoenergetic proportions in the diet. In contrast, IBAT mass and cellularity of obese >>> lean, while IBAT LPLA of lean >>> obese, suggestive of improved insulin sensitivity. These results suggest that the excess weight gain and adiposity often attributed to the consumption of excess dietary fructose sources may be at least in part a reflection of net caloric intake and insulinogenic responses rather than the type of carbohydrate consumed. In addition, the greater IBAT mass, cellularity, and percent lipid content of the obese are consistent with early onset hyperphagia and an impaired capacity for energy expenditure via non-shivering thermogenesis and thus represent a likely contributor to the epigenetic expression and development of obesity in the obese phenotype of this strain.

Dietary flaxseed and tamoxifen affect the inflammatory microenvironment in vivo in normal human breast tissue of postmenopausal women.

Anti-oestrogens such as tamoxifen, decrease the risk of breast cancer but are unsuitable for prevention because of their side-effects. Diet modifications may be a breast cancer prevention strategy. Here, we investigated if a diet addition of flaxseed, which can be converted to the phytoestrogen enterolactone by the gut microbiota, exhibited similar effects as tamoxifen on normal human breast tissue in vivo, with special emphasis on inflammatory mediators implicated in cancer progression. A total of 28 postmenopausal women were included. Thirteen women added 25 g of ground flaxseed per day and 15 were treated with tamoxifen as an adjuvant for early breast cancer for 6 weeks. Microdialysis of normal breast tissue and, as a control, in subcutaneous abdominal fat was performed for sampling of extracellular proteins in vivo before and after exposures. Enterolactone levels increased significantly after flaxseed. IL-1Ra and IL-1Ra/IL-1β ratio in the breast increased in a similar fashion after the two different treatments. Flaxseed also increased breast specific levels of IL-1RT2, IL-18 and sST2 and an overall increase of MMP-9. These changes correlated significantly with enterolactone levels. Tamoxifen decreased breast tissue levels of IL-8 and IL-18. None of the treatments induced any changes of IL-1β, IL-1RT1, IL-18BP, IL-33, IL-6, IL-6RA, MMP-1, MMP-2 and MMP-3. We conclude that dietary flaxseed and tamoxifen exert both similar and different effects, as listed above, on normal breast tissue in vivo and that a relatively modest diet change can induce significant effects on the breast microenvironment.

Fatty Acid Oxidation is Impaired in An Orthologous Mouse Model of Autosomal Dominant Polycystic Kidney Disease

BackgroundThe major gene mutated in autosomal dominant polycystic kidney disease was first identified over 20years ago, yet its function remains poorly understood. We have used a systems-based approach to examine the effects of acquired loss of Pkd1 in adult mouse kidney as it transitions from normal to cystic state. MethodsWe performed transcriptional profiling of a large set of male and female kidneys, along with metabolomics and lipidomics analyses of a subset of male kidneys. We also assessed the effects of a modest diet change on cyst progression in young cystic mice. Fatty acid oxidation and glycolytic rates were measured in five control and mutant pairs of epithelial cells. ResultsWe find that females have a significantly less severe kidney phenotype and correlate this protection with differences in lipid metabolism. We show that sex is a major determinant of the transcriptional profile of mouse kidneys and that some of this difference is due to genes involved in lipid metabolism. Pkd1 mutant mice have transcriptional profiles consistent with changes in lipid metabolism and distinct metabolite and complex lipid profiles in kidneys. We also show that cells lacking Pkd1 have an intrinsic fatty acid oxidation defect and that manipulation of lipid content of mouse chow modifies cystic disease. InterpretationOur results suggest PKD could be a disease of altered cellular metabolism.

Live well: a practical and effective low-intensity dietary counseling intervention for use in primary care patients with dyslipidemia - a randomized controlled pilot trial

BackgroundDiet is the first line of treatment for elevated cholesterol. High-intensity dietary counseling (≥360 minutes/year of contact with providers) improves blood lipids, but is expensive and unsustainable in the current healthcare settings. Low-intensity counseling trials (≤ 30 minutes/year) have demonstrated modest diet changes, but no improvement in lipids. This pilot study evaluated the feasibility and the effects on lipids and diet of a low-intensity dietary counseling intervention provided by the primary care physician (PCP), in patients at risk for cardiovascular diseases.MethodsSix month study with a three month randomized-controlled phase (group A received the intervention, group B served as controls) followed by three months of intervention in both groups.Sixty-one adults age 21 to 75 years, with LDL-cholesterol ≥ 3.37 mmol/L, possessing Internet access and active email accounts were enrolled. Diet was evaluated using the Rate-Your-Plate questionnaire. Dietary counseling was provided by the PCP during routine office visits, three months apart, using printed educational materials and a minimally interactive counseling website. Weekly emails were sent reminding participants to use the dietary counseling resources. The outcomes were changes in LDL-cholesterol, other lipid subclasses, and diet quality.ResultsAt month 3, group A (counseling started at month 1) decreased their LDL-cholesterol by −0.23 mmol/L, (−0.04 to −0.42 mmol/L, P = 0.007) and total cholesterol by −0.26 mmol/L, (−0.05 to −0.47 mmol/L, P = 0.001). At month 6, total and LDL-cholesterol in group A remained better than in group B (counseling started at month 3). Diet score in group A improved by 50.3 points (38.4 to 62.2, P < 0.001) at month 3; and increased further by 11.8 (3.5 to 20.0, P = 0.007) at month 6. Group B made the largest improvement in diet at month 6, 55 points (40.0 to 70.1, P < 0.001), after having a small but significant improvement at month 3, 22.3 points (12.9 to 31.7, P < 0.001). No significant changes occurred in HDL-cholesterol in either group.ConclusionsA low-intensity dietary counseling provided by the PCP in patients at risk for cardiovascular diseases produced clinically meaningful improvements in both diet and lipids of magnitude similar to changes reported with high intensity interventions.Trial registrationClinicalTrials.gov: NCT01695837

Ethical Naturalism and the Constitution of Agency

Neo-Aristotelian ethical naturalists generally claim that human beings need virtues, where their claim is understood to mean that human beings need virtues in order to flourish or prosper. They aim to establish a connection between goodness and flourishing for human beings. Advocates of this view must respond to the apparent possibility that we can be good human beings without flourishing or be flourishing human beings without being good. Rosalind Hursthouse argues that being virtuous is the only reliable path if we want to flourish, just as a modest diet and exercise are the only reliable way to become healthy. Yet, as Julia Annas points out, this argument is unsatisfactory. There are circumstances, such as living in a depraved society, in which it would not benefit someone to live virtuously, and it is reasonable to ask why human beings should commit themselves to virtue when the desired result, to flourish, relies on many factors that are beyond our control. In addition to the contingencies of the world, there are contingencies of our psychology. As Nietzsche and, more recently, Bernard Williams argue, it is at least equally plausible to believe that human psychology is such that instead of being fulfilled by morality, we will instead be frustrated by it. As Williams puts it, the Aristotelian view seems to presuppose an inner nisus to virtues, which is called into question by Darwinian biology, since it is ‘‘an open question whether the evolutionary success of humanity, in its extremely brief period of existence, may not rest on a rather

Vitamin and mineral supplement users. Do they have healthy or unhealthy dietary behaviours?

It is unknown whether people use vitamin and mineral supplements (VMS) to compensate for unhealthy diets, or people whom already have a healthy diet use VMS. Therefore, this study aimed to examine correlates of VMS use and whether VMS users can be categorised into specific clusters based on dietary lifestyle variables. The data used came from the Swiss Food Panel questionnaire for 2010. The sample consisted of 6189 respondents, mean age was 54 years and 47.6% were males. Data was analysed with logistic regression analysis and hierarchical cluster analysis. The results revealed that for VMS use, gender, age, education, chronic illness, health consciousness, benefits of fortification, convenience food and sugar-sweetened beverage consumption were of importance. Cluster analysis revealed three clusters (1) healthy diet, (2) unhealthy diet and (3) modest diet. Compared to non-users a higher percentage of VMS users was categorised in the healthy cluster and a lower percentage in the unhealthy cluster. More VMS-users were categorised as having an unhealthy diet (31.4%) than having a healthy diet (20.6%). The results suggest that both hypotheses-VMS are used by people with unhealthy diets and by people who least need them-hold true meaning.

A Historical Perspective of the Understanding of the Link Between Diet and Coronary Heart Disease

The development of the understanding of the underlying causes of coronary heart disease has undergone several stages. Ecological studies, such as the Seven Countries' Study, showed a possible relationship between mortality in coronary heart disease and intake of saturated fats. The investigated area with the lowest rates of cardiovascular disease was the island of Crete, Greece. A discussion soon started to evolve around the Mediterranean diet, which at the time consisted of mainly foods of vegetable origin, olive oil and cereals of unrefined nature. Several clinical trials have been undertaken since, including the Lyon Heart Diet Study where it was clearly shown that both mortality and morbidity in coronary heart disease was substantially lowered by Mediterranean food compared to controls. Dean Ornish proved that an extreme regimen actually could reduce already existing sclerotic plaques, while the WHI study showed that a more modest diet change diet not cause the intended reduction in heart disease in middle-aged women. Another prospective study of a similar age group of women showed that a diet with a low glycemic load gave a good reduction in coronary heart disease. Multiple studies of different components of food have shown no positive result, pointing at the whole diet rather than its components of nutrients being of importance. Today, the experts agree on the optimal diet to prevent not only heart disease but also cancer forms and other chronic disease such as type 2 diabetes mellitus. This diet is consisting of a lot of fruit and vegetables, lots of fish, less salt and sugar, more unrefined cereals, beans and nuts. Going from a general notion of Mediterranean food to testing that food in clinical settings and testing nutrients as preventative agents, we can conclude that a generally healthy lifestyle, including a healthy diet, appropriate amounts of physical activity, good sleep and less stress, is the way to a heart healthy life.

Impact of Exposure Measurement Error in Nutritional Epidemiology

For the past several decades, observational studies of diet and cancer have yielded many inconsistent results ( 1 ). Given the limited variation in dietary intakes within many study populations and the seemingly modest diet – cancer associations, results of such studies depend critically on an accurate assessment of the dietary exposure ( 2 ). Measurement error in exposure leads to seriously biased relative risks of cancer for dietary intakes and substantially reduces the statistical power to detect existing relationships ( 2 ). The international consortium of cohort studies known as the Pooling Project ( 3 ) aims to gain precision in relative risk estimates and overcome this loss of statistical power by combining analyses of individual data from multiple studies that examine associations between diet and cancer. In this issue of the Journal, Lee et al. ( 4 ) report the results of an analysis of fat, protein, and meat consumption in relation to the risk of renal cell cancer in 13 cohorts within the Pooling Project. Using multivariable models, they obtained null results for all of the associations they considered. In this editorial, we comment on the impact of exposure measurement error on the estimated associations between diet and disease in this and other studies. Exposure measurement error in prospective studies can usually be assumed to be nondifferential with respect to disease, that is, the relationship between the reported diet and the true diet is the same for the case subjects and the control subjects. When the exposure, but none of the confounders, is measured with error, this error attenuates the relative risk (ie, biases the relative risk toward no effect). Although statistical tests for the association remain valid, that is, they preserve the nominal statistical signifi cance level ( 5 ), the measurement error reduces the statistical power to detect the association. Consequently, the number of cases required to maintain the nominal statistical power is increased by a factor equal to the inverse-squared correlation between the reported exposure and the true exposure ( 6 ). Moreover, although adjustment for measurement error can remove existing bias in estimated relative risks, it cannot compensate for the loss of statistical power. Within the Pooling Project, the main dietary assessment instruments were study-specifi c food-frequency questionnaires (FFQs) and closely related diet histories. Most studies also included validation subsamples with multiple food records or 24-hour

Dietary Fish Oil Impairs Primary Host Resistance Against Listeria monocytogenes More than the Immunological Memory Response

The primary objective of this study was to determine whether dietary (n-3) polyunsaturated fatty acids (PUFA) impair the ability of mice to generate an immunological memory response against the bacterial pathogen, Listeria monocytogenes. Weanling BALB/c female mice were fed for 28 d one of two semipurified high fat diets containing either lard or refined menhaden fish oil, rich in long-chain (n-3) PUFA. Mice were immunized with 10(4) or 10(3) colony forming units (cfu) bacteria. Thirty-five days later, these immune mice and age-matched naïve (i.e., unimmunized) mice were challenged with 10(5) cfu bacteria. Three days postchallenge, bacterial clearance was determined. Compared with lard-fed mice, naïve mice in the fish oil treatment group had higher bacterial loads in their liver and spleen (P < 0.001). When mice were immunized with 10(4) cfu bacteria before rechallenge with 10-fold more bacteria, both lard- and fish oil-fed mice had significantly lower bacterial loads in their liver and spleen (e.g., approximately 2 log(10); P < 0.001) compared with their naïve counterparts. However, when the immunization dose was reduced to 10(3) bacteria, a modest diet treatment effect was observed, such that compared with immune lard-fed mice, immune fish oil-fed mice had significantly greater bacterial loads in their liver and spleen (i.e., approximately 0.5 log(10); P < 0.01). These data demonstrate for the first time that although dietary (n-3) PUFA can significantly impair host resistance to a primary as well as a secondary L. monocytogenes infection, the impairment of the immunological memory response is much less severe.

Back to a Future One Man's AIDS Tale Shows how Quickly Epidemic has Turned

WHEN IT WAS CALLED 'GRID': One year ago today, I told my colleagues that I was dying of AIDS. I had been fighting it for years-the illness and the telling. I had been taking AZT, and briefly even a drug given to lepers. But now I was gaunt, tired and rather sure I was losing the battle. I gave my boss an obituary I had written-I'm a features editor on Page One of The Wall Street Journal, so I certainly didn't want anybody else writing it-sent a note to my boss's boss and started saying my goodbyes. Last week, my doctor, Jerome E. Groopman, noticed that I am getting fat and said it wouldn't be a bad idea if I went on a modest diet. At age 53, I am going to the gym again. I need to buy some new clothes. I am planning to one day retire with my partner of 28 years, who is HIV-negative. What has happened in the past year, at least for me, is a miracle that couldn't have taken place at any other moment. The year 1996 is when everything changed, and very quickly, for people with AIDS. I have been grappling with this disease for nearly a decade and a half, almost since the beginning, when it was called Gay Related Immune Deficiency, or GRID. I've outlived friends and peers, and now I find myself in the unusual position of telling people how I've survived this scourge, something I never thought would happen. My condition could change for the worse tomorrow. But today I feel well again. Thanks to the arrival of the new drugs called protease inhibitors, I am probably more likely to be hit by a truck than to die of AIDS. In coming alive again, I've learned the value of a good doctor and good friends-and the importance of being honest with yourself, your co-workers and the people you love. My battle with AIDS, I'm certain, began in December 1982, at a bathhouse in Manhattan's East Village during a sexual encounter with a man whose name I didn't catch. Like other gay men, I had kept up with newspaper reports, beginning with a July 3, 1981, New York Times story with the fateful headline: "Rare Cancer Seen in 41 Homosexuals." Nevertheless, going to the baths was a big part of gay culture back then, and here I was. Old habits die hard. At the time, the federal Centers for Disease Control and medical authorities were saying little about this being an infectious disease. Indeed, they at first thought it probably wasn't. But it was pretty clear that GRID was caused either by the cumulative effects of too much sex (so many men, so many germs) or too much butyl nitrite (poppers), a sexual stimulant sniffed from little vials available for $5 at newsstands. The third possibility was that it was a sex-borne plague.

Exercise adaptation responses for gastric inhibitory polypeptide (GIP) and insulin in obese children. Possible extra-pancreatic effects.

Thirteen obese children and matched controls were fed a mixed meal, and responses were evaluated at fixed intervals for glucose, insulin, and gastric inhibitory polypeptide (GIP). The obese children were evaluated before and within 48 h after completion of a 5-mo exercise training program (ETP). The ETP included three aerobic exercise sessions per week and modest diet restrictions. Caloric expenditure was increased by approximately 300 kcal/exercise session. Weight gain was minimal over the 5 mo. An unexpected increase in GIP response and improved insulin tolerance were recorded for the obese children post-ETP. GIP values were higher (P less than 0.05) at 30 and 60 min and led to a highly significant elevation (P less than 0.01) of the integrated GIP response for post-ETP obese versus both pre-ETP and normal-weight controls. Insulin values were lower (P less than 0.05) at 30 and 60 min and led to a lower integrated insulin response (P less than 0.0585) for post-ETP obese children. However, the obese children continued to secrete more insulin (P less than 0.05) than normal-weight controls. Glucose tolerance, similar for pre-ETP obese subjects and controls, did not change in post-ETP children. Exercise-induced improvement in glucose utilization in these obese children was associated with an increase in GIP secretion. This contrasts with reports that calorie restriction will improve glucose utilization with decreased insulin and GIP secretion. The study demonstrates a previously unreported uncoupling of GIP and insulin secretion and suggests shifts in peripheral tissue sensitivity to insulin-induced glucose uptake. These shifts may, in part, be influenced by GIP.