Characterization of Activation of the Hypothalamic-Pituitary-Adrenal Axis by the Herbicide Atrazine in the Female Rat.

Atrazine (ATR) is a commonly used pre-emergence and early postemergence herbicide. Rats gavaged with ATR and its chlorometabolites desethylatrazine (DEA) and deisopropylatrazine (DIA) respond with a rapid and dose-dependent rise in plasma corticosterone, whereas the major chlorometabolite, diaminochlorotriazine (DACT), has little or no effect on corticosterone levels. In this study, we investigated the possible sites of ATR activation of the hypothalamic-pituitary-adrenal (HPA) axis. ATR treatment had no effect on adrenal weights but altered adrenal morphology. Hypophysectomized rats or rats under dexamethasone suppression did not respond to ATR treatment, suggesting that ATR does not directly stimulate the adrenal gland to induce corticosterone synthesis. Immortalized mouse corticotrophs (AtT-20) and primary rat pituitary cultures were treated with ATR, DEA, DIA, or DACT. None of the compounds induced an increase in ACTH secretion or potentiated ACTH release in conjunction with CRH on ACTH release. In female rats gavaged with ATR, pretreatment with the CRH receptor antagonist astressin completely blocked the ATR-induced rise in corticosterone concentrations, implicating CRH release in ATR-induced HPA activation. Intracerebroventricular infusion of ATR, DEA, and DIA but not DACT at concentrations equivalent to peak plasma concentrations after gavage dosing resulted in an elevation of plasma corticosterone concentrations. However, ATR did not induce c-Fos immunoreactivity in the paraventricular nucleus of the hypothalamus. These results indicate that ATR activates the HPA axis centrally and requires CRH receptor activation, but it does not stimulate cellular pathways associated with CRH neuronal excitation.

The Diet of Inmates: An Analysis of a 28-Day Cycle Menu Used in a Large County Jail in the State of Georgia.

Given the many well-documented relationships between diet and health, growing medical care expenses for those incarcerated, and limited information on foods served in correctional facilities, this study examined the nutritional adequacy of a 28-day cycle menu used in a large county jail in Georgia. When compared with Dietary Reference Intakes, provisions of energy (female inmates only), sodium, saturated fat, and cholesterol exceeded recommendations. Magnesium, potassium, and vitamins A, D, and E met less than two thirds of recommendations. Compared with MyPlate recommendations, grains were overrepresented, while vegetables, fruits, and dairy were underrepresented in the menu. Small menu changes could improve the menu's nutrient content and potentially increase inmates' health and well-being.

The pancreas-brain axis: insight into disrupted mechanisms associating type 2 diabetes and Alzheimer's disease.

Epidemiological and observational studies indicate a positive correlation between type 2 diabetes (T2DM) and dementia, with an increased risk of dementia and Alzheimer's disease (AD) associated with insulin-treated diabetes patients. The purpose of this review is to reveal the molecular mechanisms that connect physiological and pathological processes commonly observed in T2DM and AD. Conformational modifications in peptide residues, such as amyloid-ß peptide in AD and amylin in T2DM have been shown to instigate formation of insoluble protein aggregates that get deposited in extracellular spaces of brain and pancreatic tissue thus disrupting their normal function. Impaired insulin signaling plays a critical role in AD pathogenesis by reducing IRS-associated PI3 kinase activity and increasing GSK-3ß activity. GSK-3ß has been suggested to be a component of the γ-secretase complex and is involved in amyloid-ß protein precursor processing. GSK-3ß along with CDK5 is responsible for hyperphosphorylation of tau leading to the formation of neurofibrillary tangles. In summary, there is evidence to believe that a molecular link connects AD and T2DM and has potential for further investigation toward development of an effective therapeutic target.

Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice.

AIMS: To determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. MATERIALS AND METHODS: Male C57BL/6 mice were placed on a control or high-fat diet (HFD) and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2 (-/-) (niacin receptor(-/-)) mice. RESULTS: Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2 (-/-) mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARγ C/EBPα or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription) in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lα, or DsbA-L (key ER chaperones involved in adiponectin production and secretion). However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1ß in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. CONCLUSIONS: Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expression in a niacin receptor-dependent manner.

Signaling proteins that influence energy intake may affect unintentional weight loss in elderly persons.

After age 70 to 75 years, average body weight decreases both in ailing and healthy people because of a loss of appetite that results in reduced energy intake and the loss of body fat and lean muscle tissue. This so-called anorexia of aging predisposes elderly people to continued pathologic weight loss and malnutrition-major causes of morbidity and mortality. Health care professionals must understand the many factors involved in the anorexia of aging to help older adults prevent unintentional weight loss. Psychological, social, and cultural factors are important effectors; however, physiological factors are emphasized here because they are not thoroughly understood and they make it inherently difficult for most people to alter their body weight. Monoamines, steroid hormones (glucocorticoids and mineralocorticoids), endocannabinoids, and proteins all influence body weight. This review is an analysis of proteins from the brain, pancreas, adipose tissue, and gastrointestinal tract that are known to affect energy intake and energy balance, with an attempt to identify those factors that may change with aging. The articles included in this review were obtained by a PubMed database search using the keywords mouse OR rat OR human AND aged OR aging OR older OR elderly AND adult AND anorexia OR "unintentional weight loss," and each of the individual proteins discussed, as well as from the reference lists of those articles. The results reveal that some proteins may be important in the development of unintentional weight loss in elderly persons, whereas others may not have a significant role. However, many of the proteins that could conceivably have a role in unintentional weight loss have not yet been studied with that question in mind. Preventing unintentional weight loss in older adults is an important goal and further research on the role of proteins important for the maintenance of energy balance and the development of unintentional weight loss in elderly persons is warranted.

The influence of habitual exercise training and meal form on diet-induced thermogenesis in college-age men.

This study compared type of habitual exercise and meal form on diet-induced thermogenesis (DIT) in 29 men age 19-28 yr. Resting metabolic rate (RMR) and DIT response to solid-meal (bar) vs. liquid-meal (shake) ingestion were measured via indirect calorimetry; classifications were sedentary (n = 9), endurance trained (n = 11), or resistance trained (n = 9). Height, weight, and body composition (using bioelectrical impedance) were measured for each subject. Energy expenditure was determined before and every 30 min after meal consumption for 210 min. RMR was significantly (p = .045) higher in the endurance- and resistance-trained groups. However, when expressed per kilogram fat-free mass (FFM; relative RMR), differences were not significant. Both DIT (kcal/min) and relative DIT (kcal · min-1 · kg FFM-1) significantly increased with time (p < .0001) from RMR for each meal form. There was no significant exercise-group effect on DIT or relative DIT. There was a significant (p = .012) effect of meal form on DIT; shakes elicited a higher DIT. This significant difference was not found for relative DIT. There was a significant interaction between group and meal form for DIT (p = .008) and relative DIT (p < .0001). Shakes elicited a significantly greater DIT (p = .0002) and relative DIT (p = .0001) in the resistance-trained group. In the sedentary group, relative DIT from shakes was significantly lower than from bars (p = .019). In conclusion, habitual exercise appears to increase RMR, and meal form may impart changes in relative DIT depending on exercise status.

Guanethidine treatment does not block the ability of central leptin administration to decrease blood glucose concentrations in streptozotocin-induced diabetic rats.

Leptin, administered either into the ventricles of the brain or systemically, has been shown to normalize blood glucose concentrations in streptozotocin (STZ)-induced diabetic rats. We hypothesized that an intact sympathetic nervous system is necessary for centrally administered leptin to normalize or attenuate high blood glucose concentrations in STZ-induced diabetic rats. Young male Wistar rats (approximately 50 g) were treated every other day with either s.c. guanethidine (100 mg/kg) or vehicle for 2 weeks. Rats were then implanted with an intracerebroventricular cannula directed to the lateral ventricle and made diabetic with an i.v. injection of STZ (50 mg/kg). Half of the animals in each group were given daily injections of leptin (10 microl), while the remaining animals received vehicle injections. Blood glucose concentrations were measured daily and tissue norepinephrine content was determined by high performance liquid chromatography at the end of the study. Guanethidine pretreatment did not block the ability of centrally administered leptin to decrease blood glucose concentrations in diabetic rats. This suggests that the sympathetic nervous system does not mediate the leptin-induced attenuation of high blood glucose concentrations observed in diabetic rats.

Plasma phenylalanine concentrations are associated with hepatic iron content in a murine model for phenylketonuria.

Individuals with phenylketonuria (PKU) have been reported to have altered trace mineral status. In this study, we evaluated in a murine PKU model whether protein level and level of phenylalanine (PHE) restriction could modulate iron, copper, and zinc status. Fifty-four male weanling PKU and control mice were assigned to receive for 56 days an elemental low or normal protein diet; PKU mice also were assigned to receive PHE restriction (treated) or no restriction (untreated). PHE-restricted mice consumed a prescribed dietary PHE to maintain plasma PHE concentrations between 120 and 480 micromol/L. PHE-unrestricted and control mice received equal amounts of dietary PHE. Intestinal and hepatic copper, iron, and zinc were measured at day 56 and fecal minerals measured at baseline and day 56. Mean plasma PHE concentrations were significantly greater in PKU PHE-unrestricted versus PKU PHE-restricted mice and control mice. Mean intestinal weights when normalized for body weight were significantly greater in PKU mice versus control mice. PKU PHE-unrestricted mice had significantly lower hepatic copper and zinc than PKU PHE-restricted mice, and significantly greater hepatic iron than control and PKU PHE-restricted mice. PKU PHE-unrestricted mice on a low protein diet had hepatic iron concentrations about 1.5 times that of the other mice. Fecal iron concentrations in all mice were significantly greater at day 56 than at baseline. No animal group effects or protein level effects were found for fecal copper, iron, or zinc contents. We conclude that hyperphenylalaninemia alters the metabolism of iron, copper, and zinc in PKU mice.

Non-anemic iron depletion, oral iron supplementation and indices of copper status in college-aged females.

OBJECTIVES: Indices of copper status, specifically serum copper and ceruloplasmin concentrations and erythrocyte superoxide dismutase activity, and iron status, including serum ferritin, transferrin receptors, hemoglobin and hematocrit, were studied in 27 college-aged females with adequate iron versus low iron stores. METHODS: Serum copper and ceruloplasmin concentrations, erythrocyte superoxide dismutase activity, serum ferritin, transferrin receptors, hemoglobin and hematocrit were studied in 15 females with non-anemic iron depletion before and after five weeks of iron supplementation and in 12 healthy iron-adequate females aged 19 to 28 years. RESULTS: Mean hemoglobin, hematocrit and ferritin concentrations of the control group (144 +/- 11 g/L, 43 +/- 3% and 38 +/- 15 micro g/L, respectively) were significantly higher than those of the iron depleted group prior to supplementation (134 +/- 9 g/L, 39 +/- 2% and 11 +/- 6 micro g/L, respectively). The serum transferrin receptor to serum ferritin ratio was significantly greater for the iron depleted group prior to supplementation (890 +/- 753) versus the control group (151 +/- 61). Mean serum copper and ceruloplasmin concentrations and erythrocyte superoxide dismutase activity of the iron-adequate control group (20.0 +/- 5.7 micro mol/L, 463 +/- 142 mg/L and 527 +/- 124 U/mL, respectively) were significantly higher than those of the iron depleted group (12.4 +/- 3.8 micro mol/L, 350 +/- 108 mg/L and 353 +/- 186 U/mL, respectively) prior to supplementation. Following iron supplementation, hematocrit and ferritin concentrations of the iron depleted group significantly increased to 42 +/- 3% and 26 +/- 8 micro g/L, respectively. Mean serum transferrin receptor concentrations and the serum transferrin receptor to ferritin ratios significantly decreased in the iron depleted group following supplementation (6.1 +/- 1.6 mg/L to 4.6 +/- 1.5 mg/L and 890 +/- 753 to 198 +/- 114, respectively). Iron supplementation also significantly increased the mean serum copper concentration to 14.2 +/- 5.4 micro mol/L and, in subjects with serum ferritin concentrations

Central leptin increases insulin sensitivity in streptozotocin-induced diabetic rats.

This study examined the effect of intracerebroventricular leptin on insulin sensitivity in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were cannulated in the lateral ventricle and, after recovery, administered either intravenous STZ (50 mg/kg) to induce diabetes or citrate buffer. Chronic leptin (10 microg/10 microl icv) or vehicle injections were administered daily for 14 days beginning 2 days after establishment of hyperglycemia in the diabetic animals. At the end of the 2 wk of injections, insulin sensitivity was measured by the steady-state plasma glucose (SSPG) method. Blood glucose concentrations were dramatically reduced and normalized by the 4th day in diabetic animals receiving intracerebroventricular leptin treatment. Diabetic animals exhibited insulin resistance, whereas intracerebroventricular leptin significantly enhanced insulin sensitivity, as indicated by decreased SSPG. Circulating leptin levels were not increased in animals injected with intracerebroventricular leptin. Thus the increased peripheral insulin sensitivity appears to be due solely to the presence of leptin in the brain, not to leptin acting peripherally. These data imply that inadequate central leptin signaling may lead to insulin resistance.