Differential weight loss with intermittent fasting or daily calorie restriction in low- and high-fitness phenotypes.

NEW FINDINGS: What is the central question of this study? How does intrinsic aerobic capacity impact weight loss with 50% daily caloric restriction and alternate-day fasting? What is the main finding and its importance? Intermittent fasting is effective for weight loss in rats with low fitness, which highlights the importance of how intermittent fasting interacts with aerobic fitness. ABSTRACT: Recent interest has focused on the benefits of time-restricted feeding strategies, including intermittent fasting, for weight loss. It is not yet known whether intermittent fasting is more effective than daily caloric restriction at stimulating weight loss and how each is subject to individual differences. Here, rat models of leanness and obesity, artificially selected for intrinsically high (HCR) and low (LCR) aerobic capacity, were subjected to intermittent fasting and 50% calorie restrictive diets in two separate experiments using male rats. The lean, high-fitness HCR and obesity-prone, low-fitness LCR rats underwent 50% caloric restriction while body weight and composition were monitored. The low-fitness LCR rats were better able to retain lean mass than the high-fitness HCR rats, without significantly different proportional loss of weight or fat. In a separate experiment using intermittent fasting in male HCR and LCR rats, alternate-day fasting induced significantly greater loss of weight and fat mass in LCR compared with HCR rats, although the HCR rats had a more marked reduction in ad libitum daily food intake. Altogether, this suggests that intermittent fasting is an effective weight-loss strategy for those with low intrinsic aerobic fitness; however, direct comparison of caloric restriction and intermittent fasting is warranted to determine any differential effects on energy expenditure in lean and obesity-prone phenotypes.

Author Correction: Physical Activity, Energy Expenditure, and Defense of Body Weight in Melanocortin 4 Receptor-Deficient Male Rats.

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Physical Activity, Energy Expenditure, and Defense of Body Weight in Melanocortin 4 Receptor-Deficient Male Rats.

Melanocortin 4 receptor (MC4R) variants contribute to human obesity, and rats lacking functional MC4R (Mc4rK314X/K314X) are obese. We investigated the hypothesis that low energy expenditure (EE) and physical activity contribute to this obese phenotype in male rats, and determined whether lack of functional MC4R conferred protection from weight loss during 50% calorie restriction. Though Mc4rK314X/K314X rats showed low brown adipose Ucp1 expression and were less physically active than rats heterozygous for the mutation (Mc4r+/K314X) or wild-type (Mc4r+/+) rats, we found no evidence of lowered EE in Mc4rK314X/K314X rats once body weight was taken into account using covariance. Mc4rK314X/K314X rats had a significantly higher respiratory exchange ratio. Compared to Mc4r+/+ rats, Mc4rK314X/K314X and Mc4r+/K314X rats lost less lean mass during calorie restriction, and less body mass when baseline weight was accounted for. Limited regional overexpression of Mc3r was found in the hypothalamus. Although lower physical activity levels in rats with nonfunctional MC4R did not result in lower total EE during free-fed conditions, rats lacking one or two functional copies of Mc4r showed conservation of mass, particularly lean mass, during energy restriction. This suggests that variants affecting MC4R function may contribute to individual differences in the metabolic response to food restriction.

New questions and insights into nitrate/nitrite and human health effects: a retrospective cohort study of private well users' immunological and wellness status.

The retrospective cohort study described in this article examined 150 Iowa private well users' (aged 1-60 years) drinking water below the 10 parts per million nitrate-nitrogen (nitrate-N) maximum contaminant level and analyzed health history data and blood samples including hemoglobin fractions and immunological parameters. Positive associations existed (bivariate fit) between higher nitrate exposure and body mass index, lower recreational activity, perceived poorer health, and perceptions of susceptibility to illness. A directly proportionate relationship was seen between methemoglobin level in the blood and nitrate ingestion. High tumor necrosis factor-beta (TNF-beta) expression was also seen (bivariate fit, f = 3.76, p = .05). Complaints of stomach/ intestinal difficulties (heartburn/reflux > 50%; f = 5.274, p = .0231) and bone, muscle, and nerve complaints (osteoarthritis [rheumatoid excluded] = 47%; f = 6.0533, p = .0150) were found with increasing nitrate exposure. In vivo exposures of nitrate-N associated with complaints of bone/joint disorders or with altered ex vivo production of TNF-beta or Th2/Treg cytokine interleukin-10 have not been previously illustrated with environmental exposures.

Mechanisms of cancer prevention by green and black tea polyphenols.

Drinking green tea is associated with decreased frequency of cancer development. This review outlines the wide range of mechanisms by which epigallocatechin gallate (ECGC) and other green and black tea polyphenols inhibit cancer cell survival. EGCG suppressed androgen receptor expression and signalling via several growth factor receptors. Cell cycle arrest or apoptosis involved caspase activation and altered Bcl-2 family member expression. EGCG inhibited telomerase activity and led to telomere fragmentation. While at high concentrations polyphenols had pro-oxidative activities, at much lower levels, anti-oxidative effects occurred. Nitric oxide production was reduced by EGCG and black tea theaflavins by suppressing inducible nitric oxide synthase via blocking nuclear translocation of the transcription factor nuclear factor-kappaB as a result of decreased IkappaB kinase activity. Polyphenols up- or down-regulated activity of a number of key enzymes, including mitogen-activated protein kinases and protein kinase C, and increased or decreased protein/mRNA levels, including that of cyclins, oncogenes, and tumor suppressor genes. Metastasis was inhibited via effects on urokinase and matrix metalloproteinases. Polyphenols reduced angiogenesis, in part by decreasing vascular endothelial growth factor production and receptor phosphorylation. Recent work demonstrated that EGCG reduced dihydrofolate reductase activity, which would affect nucleic acid and protein synthesis. It also acted as an aryl hydrocarbon receptor an-tagonist by directly binding the receptor's molecular chaperone, heat shock protein 90. In conclusion, green and black tea polyphenols act at numerous points regulating cancer cell growth, survival, and metastasis, including effects at the DNA, RNA, and protein levels.

Low-level atrazine exposure decreases cell proliferation in human fibroblasts.

There is continuing concern that release of certain chemicals into the environment leads to human exposure to toxins, particularly through contaminated ground and surface waters. The triazine herbicide atrazine (2-chloro-4-ethylamine-6-isopropylamino-S-triazine) is routinely found as a contaminant in many surface and groundwaters. Little is known of the long-term effects of atrazine exposure on human cells. The objective of this research was to examine whether low-level exposure of atrazine to normal human fibroblast cells in culture had measurable deleterious effects. We show that low-level, short-term exposure of atrazine to normal fibroblasts results in decreased cell proliferation. In two separate assays to measure cell proliferation, either a 1.5-fold decrease in the cell number occurred (saturation density analysis) or a 2-fold decrease in cell proliferation was found (MTT analysis). Experiments to measure apoptosis in cells exposed to low levels of atrazine did not show DNA fragmentation or increased caspase activity. Thus, this analysis shows that short-term exposure to environmentally relevant, low levels of atrazine can be assessed by a decrease in cellular proliferation of normal human cells.