B. Douglas White

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-1β 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.

TRAF6 and p62 inhibit amyloid β-induced neuronal death through p75 neurotrophin receptor.

Amyloid β (Aβ) aggregates are the primary component of senile plaques in Alzheimer disease (AD) patients brain. Aβ is known to bind p75 neurotrophin receptor (p75(NTR)) and mediates Aβ-induced neuronal death. Recently, we showed that NGF leads to p75(NTR) polyubiquitination, which promotes neuronal cell survival. Here, we demonstrate that Aβ stimulation impaired the p75(NTR) polyubiquitination. TRAF6 and p62 are required for polyubiquitination of p75(NTR) on NGF stimulation. Interestingly, we found that overexpression of TRAF6/p62 restored p75(NTR) polyubiquitination upon Aβ/NGF treatment. Aβ significantly reduced NF-κB activity by attenuating the interaction of p75(NTR) with IKKβ. p75(NTR) increased NF-κB activity by recruiting TRAF6/p62, which thereby mediated cell survival. These findings indicate that TRAF6/p62 abrogated the Aβ-mediated inhibition of p75(NTR) polyubiquitination and restored neuronal cell survival.

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 μg/L, respectively) were significantly higher than those of the iron depleted group prior to supplementation (134 ± 9 g/L, 39 ± 2% and 11 ± 6 μg/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 μmol/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 μmol/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 μg/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 μmol/L and, in subjects with serum ferritin concentrations ≤12 μg/L, the mean serum ceruloplasmin concentration. Conclusions: Non-anemic iron depletion characterized by low iron stores is associated with negative impacts on copper status. Iron supplements improved indices of iron status and serum copper and ceruloplasmin concentrations. Whether the diminished serum copper and ceruloplasmin concentrations and superoxide dismutase activity are associated with free radical damage to iron depleted cells requires further investigation.

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 Alzheimers 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-β 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-3β activity. GSK-3β has been suggested to be a component of the γ-secretase complex and is involved in amyloid-β protein precursor processing. GSK-3β 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.

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.

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 impact of physical activity on body weight and fat gains during the first 3 years of college

Over two-thirds of students gain weight and body fat during college, especially during the freshman year. This study examined whether participation in physical activity during the first 3 years of college was associated with favorable changes in body weight and percent body fat. Participants included 535 college students (345 females, 190 males). Height and weight (assessed by standard techniques) and body fat (assessed by bioelectrical impedance analysis) were obtained at the beginning of fall semester and at the end of spring semester of each year; in addition during the first 2 years, assessments were also conducted at the end of fall semester for a total of eight assessments between 2007 and 2010. Physical activity participation was self-reported using a questionnaire that included a subset of questions from the National College Health Risk Behavior Survey. While both males and females exhibited significant increases in weight and percent body fat over the 3-year period; for the females, participation in strength training was associated with loss of weight and percent body fat. The results of this study emphasize the benefits of physical activity, especially strength training, for college females as a means to reduce or prevent body weight and fat gains during the first 3 years of college.

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.