Dietary fibre intake in childhood or adolescence and subsequent health outcomes: A systematic review of prospective observational studies.

AIM: To determine whether higher fibre intakes during childhood or adolescence effect a broad range of intermediate markers of cardiometabolic risk or other health related issues. MATERIALS AND METHODS: We used online searches up to January 2020 and manual searches to identify prospective observational studies reporting on childhood or adolescent intakes of dietary fibre, vegetables, fruit and refined or whole grains. Outcomes measured later in life were body weight, blood lipids, blood pressure, glycaemia, bone health, cognition, growth and bowel habits. Potential age-specific ranges for dietary fibre were extrapolated from published adult data. RESULTS: We identified 45 publications reporting on 44 354 participants from 30 cohort studies. Mean age at dietary assessment varied from 1 to 19.3 years. Follow-up duration varied from 4 months to 27 years. Although well-conducted studies reported improvements in body weight, blood lipids and glycaemia, the diverse nature of studies precluded meta analysis. The quality of evidence was very low to low given the limited data available per outcome and the inability to synthesize results from multiple studies. Potential dietary fibre intake begins at 13-16 g a day for 2-year-olds and increases until the age of 10 years, when values are comparable with an adult range of 25-30 g a day. CONCLUSIONS: Given the inconsistency in findings from cohort studies other than an absence of detrimental effects, it seems appropriate that recommendations regarding childhood fibre intake are extrapolated from relevant adult data.

Toward revising dietary zinc recommendations for children aged 0 to 3 years: a systematic review and meta-analysis of zinc absorption, excretion, and requirements for growth.

CONTEXT: The Food and Agriculture Organization of the United Nations and the World Health Organization are updating their dietary zinc recommendations for children aged 0 to 3 years. OBJECTIVE: The aim of this review was to retrieve and synthesize evidence regarding zinc needs for growth as well as zinc losses, absorption, and bioavailability from the diet. DATA SOURCES: MEDLINE, Embase, and Cochrane Library databases were searched electronically from inception to August 2020. Studies assessing the above factors in healthy children aged 0 to 9 years were included, with no limits on study design or language. DATA EXTRACTION: Ninety-four studies reporting on zinc content in tissue (n = 27); zinc absorption (n = 47); factors affecting zinc bioavailability (n = 30); and endogenous zinc losses via urine, feces, or integument (n = 40) met the inclusion criteria. Four reviewers extracted data and two reviewers checked for accuracy. DATA ANALYSES: Studies were synthesized narratively, and meta-analyses of zinc losses and gains as well the subgroups of age, type of feeding, country's income, and molar ratio of phytate to zinc were conducted. Meta-analysis revealed an overall mean (95%CI) urinary and endogenous fecal zinc excretion of 17.48 µg/kg/d (11.80-23.15; I2 = 94%) and 0.07 mg/kg/d (0.06-0.08; I2 = 82%), respectively, with a mean fractional zinc absorption of 26.75% (23.69-29.81; I2 = 99%). Subgrouping by age revealed differences in mean values associated with the transition from milk-based diets to solid food during the first 3 years of life. CONCLUSION: This review synthesizes data that may be used to formulate zinc requirements in young children. Results should be interpreted with caution because of considerable heterogeneity in the evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020215236.

Adverse Effects of Excessive Zinc Intake in Infants and Children Aged 0-3 Years: A Systematic Review and Meta-Analysis.

Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.

Cellular program controlling the recovery of adipose tissue mass: An in vivo imaging approach.

The cellular program responsible for the restoration of adipose tissue mass after weight loss is largely uncharacterized. Leptin mRNA levels are highly correlated with adipose tissue mass, and leptin expression can thus be used as a surrogate for changes in the amount of adipose tissue. To further study the responses of adipocytes to changes in weight, we created a transgenic mouse expressing the luciferase reporter gene under the control of leptin regulatory sequences, which allows noninvasive imaging of the leptin expression of mice in vivo. We used these animals to show that weight loss induced by fasting or leptin treatment results in the retention of lipid-depleted adipocytes in adipose depots. To further study the cellular response to weight regain after leptin treatment, a leptin withdrawal protocol was used to induce a state of acute leptin deficiency in wild type mice. Acute leptin deficiency led to the transient deposition of large amounts of glycogen within pre-existing, lipid-depleted adipocytes. This was followed by rapid reaccumulation of lipid. Transcriptional profiling revealed that this cellular response was associated with induction of mRNAs for the entire pathway of enzymes necessary to convert glucose into acetyl-CoA and glycerol, key substrates for the synthesis of triglycerides.

Health effects of saturated and trans-fatty acid intake in children and adolescents: Systematic review and meta-analysis.

BACKGROUND: Elevated cholesterol has been linked to cardiovascular disease in adults and preclinical markers of atherosclerosis in children, thus reducing saturated (SFA) and trans-fatty acids (TFA) intake from an early age may help to reduce cholesterol and the risk of cardiovascular disease later in life. The aim of this review is to examine the evidence for health effects associated with reducing SFA and TFA intake in free-living children, adolescents and young adults between 2 to 19 years of age. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective cohort studies. Study selection, assessment, validity, data extraction, and analysis were undertaken as specified by the Cochrane Collaboration and the GRADE working group. Data were pooled using inverse variance models with random effects. DATA SOURCES: EMBASE; PubMed; Cochrane Central Register of Controlled Trials; LILACS; and WHO Clinical Trial Registry (up to July 2016). ELIGIBILITY CRITERIA FOR SELECTING TRIALS: RCTs involving dietary interventions aiming to reduce SFA or TFA intakes and a control group, and cohort studies reporting the effects of SFA or TFA exposures, on outcomes including blood lipids; measures of growth; blood pressure; insulin resistance; and potential adverse effects. Minimum duration was 13 days for RCTs and one year for cohort studies. Trials of weight loss or confounded by additional medical or lifestyle interventions were excluded. RESULTS: Compared with control diets, there was a highly statistically significant effect of reduced SFA intake on total cholesterol (mean difference (MD) -0.16 mmol/l, [95% confidence interval (CI): -0.25 to -0.07]), LDL cholesterol (MD -0.13 mmol/l [95% CI:-0.22 to -0.03]) and diastolic blood pressure (MD -1.45 mmol/l [95% CI:-2.34 to -0.56]). There were no significant effects on any other risk factors and no evidence of adverse effects. CONCLUSIONS: Advice to reduce saturated fatty acids intake of children results in a significant reduction in total and LDL-cholesterol levels as well as diastolic blood pressure without evidence of adverse effects on growth and development. Dietary guidelines for children and adolescents should continue to recommend diets low in saturated fat.

Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter.

The melanocortin-4 receptor (MC4-R) is an important regulator of energy homeostasis, and evidence suggests that MC4-R-expressing neurons are downstream targets of leptin action. MC4-Rs are broadly expressed in the CNS, and the distribution of MC4-R mRNA has been analyzed most extensively in the rat. However, relatively little is known concerning chemical profiles of MC4-R-expressing neurons. The extent to which central melanocortins act presynaptically or postsynaptically on MC4-Rs is also unknown. To address these issues, we have generated a transgenic mouse line expressing green fluorescent protein (GFP) under the control of the MC4-R promoter, using a modified bacterial artificial chromosome. We have confirmed that the CNS distribution of GFP-producing cells is identical to that of MC4-R mRNA in wild-type mice and that nearly all GFP-producing cells coexpress MC4-R mRNA. For example, cells coexpressing GFP and MC4-R mRNA were distributed in the paraventricular hypothalamic nucleus (PVH) and the dorsal motor nucleus of the vagus (DMV). MC4-R promotor-driven GFP expression was found in PVH cells producing thyrotropin-releasing hormone and in cholinergic DMV cells. Finally, we have observed that a synthetic MC3/4-R agonist, MT-II, depolarizes some GFP-expressing cells, suggesting that MC4-Rs function postsynaptically in some instances and may function presynaptically in others. These studies extend our knowledge of the distribution and function of the MC4-R. The transgenic mouse line should be useful for future studies on the role of melanocortin signaling in regulating feeding behavior and autonomic homeostasis.

Regulation of T cell-mediated hepatic inflammation by adiponectin and leptin.

Concanavalin A-induced hepatotoxicity was compared in lipodystrophic aP2-nSREBP-1c transgenic mice (LD mice) lacking adipose tissue, obese leptin-deficient ob/ob mice, and lean wild-type (WT) mice. Serum leptin and adiponectin were low in LD mice, whereas ob/ob mice had undetectable leptin, but high adiponectin. Protection from hepatotoxicity was observed in ob/ob, but not in LD mice, despite low cytokine levels and reduced T cell activation and hepatic natural killer T cells in both groups. Administration of adiponectin protected LD mice from hepatotoxicity without altering cytokine levels. In contrast, administration of leptin heightened disease susceptibility by restoring cytokine production. Neutralization of TNF alpha protected LD mice from liver damage. Increased in vivo susceptibility to the hepatotoxic effect of TNF alpha was observed in LD mice. In vitro, adiponectin protected primary hepatocytes from TNF alpha-induced death, whereas leptin had no protective effect. In conclusion, although leptin increases susceptibility to hepatotoxicity by regulating cytokine production and T cell activation, adiponectin protects hepatocytes from TNF alpha-induced death.

Acute leptin deficiency, leptin resistance, and the physiologic response to leptin withdrawal.

Food restriction and weight loss result in reduced plasma leptin, which is associated with a pleiotropic biologic response. However, because weight loss itself is also associated with changes in numerous other humoral and metabolic signals, it can be difficult to determine the precise features of the biologic response to acute leptin deficiency. To study this response in the absence of changes in nutritional state, we have developed a protocol that allows such analysis in normal, non-food-restricted animals. Wild-type mice are treated with high-dose leptin until fat mass is depleted and, as a consequence, endogenous leptin production is reduced. At this point, exogenous leptin is abruptly withdrawn, thus inducing a state of leptin deficiency in otherwise normal mice. Leptin deficiency is sustained by feeding the animals only as much as they consumed voluntarily before leptin withdrawal. The biologic response to leptin deficiency induced in this manner includes altered neuropeptide levels, decreased energy expenditure, and impaired reproductive and immune function. Replacement of leptin at physiological concentrations after withdrawal of high-dosage leptin blunts, but does not completely block, the hyperphagia and weight regain caused by acute leptin deficiency, nor does it correct the resulting reproductive and immune dysfunction. This suggests that high-dosage leptin treatment induces a state of partial leptin resistance. In aggregate, these studies establish the role of acute hypoleptinemia in regulating energy balance, the immune system, and reproductive function, and further suggest that high-dosage leptin treatment can induce a state of acquired leptin resistance.