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International Obesity taskforce

Jamie Oliver's Food Revolution

 

Enhanced links are provided by Childhood obesity books ..........

As with all risk factors, these do not cause obesity: they add an element of risk and may act in synergy with other risk factors or susceptibility genes. Their risk promoting ability may be increased or decreased by these other factors.

Environmental risk factors and medical conditions associated with Childhood obesity

Ongoing clinical trails, worldwide, can be interrogated at ClinicalTrials.Gov a service of the US National Institutes of Health

 

 

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Genes: It is often difficult to separate traits (for example lipid levels) from obesity, or genetically distinguish obesity from body mass index, size, growth etc, or to distinguish obesity from childhood obesity: These genes have been associated with obesity and sometimes with underlying traits. As with most genetic (and risk factor) studies, associations are often contested.

Obesity syndromes Alström Syndrome: ALSMS1 (OMIM) Prader-Willi syndrome MAGEL2 SNRPN (OMIM)

ABO ACP1 ADIPOQ ADRB1 ADRB2 AMD1 APOA5 APOB APOE ARHGAP11A BBS4 BCDIN3D BBS6 BDNF CCR3 CHRNA3 CNR1 CRHR1 COL4A1 CRP DARC ENPP1 ESR1 FAIM2 FAAH FABP4 FLJ35579 . FOXE1 FTO GAD2 GCKR . GHRL |GNPDA2 IGFBP3 IL6 IL15 INADL INSIG2 INS KCTD15 LEP LEPR LPIN1 LPL LRRN6C MAF MATK MC3R MC4R MMP2 MMP9 MRSA MTCH2 MTNR1B NAMPT NEGR1 NMU NNAT NOS3 NPPA NPC1 NR0B2 NRXN3 NPY2R PCSK1 PCSK2 PNPLA1 PNPLA3 POMC PON1 PPARG PRF1 PTER PTP1B PYY SEC16B SERPINE1 SH2B1 . SP7 TFAP2B TMEM18 TNF UCP1 UCP2 UCP3 VEGF XPA

GWAS Genome.gov

BMPR1A INSIG2, FTO, MC4R, TMEM18, GNPDA2, NEGR1, BDNF, KCTD15 and 1q25 Zhao et al, 2009 BDNF FTO TMEM18 NRXN3 MC4R SEC16B GNPDA2 TNNI3K QPCTL Zhao et al, 2011 BCIN3D BDNF GNPDA2 KCTD15 LYPLAL1 MC4R NEGR1 SEC16B TFAP2B TMEM18 den Hoed et al 2010 HOXB5 OLFM4 Bradfield et al, 2012

Adult FTO ZNF248 RTN4 ITPR3 TRAM1L1 MUC15 FBN2 RARB PRF1 C20orf133 MLN RAFTLIN FLJ20309 (Cotsapas et al, 2009)

Copy number variation Deletion ABCB5 EDIL3 FOXP2 S1PR5 TBCA ZPLD1 Duplication ARL15 KIF2B Glessner et al, 2010

Methylation NOS3 RXRA

GeneXenvironment

The association between FAIM2 , NPC1, FTO , MC4R or BDNF and obesity risk was only observed in children who had moderate-to-low physical activity levels or engaged in sedentary behavior, regardless of which risk alleles they carried.Xi et al, 2011 See also Beyerlein et al, 2011

For KEGG pathways Yellow = obesity genes: Blue = compounds whose levels change, or which are toxic (glutamate/fructose)

Need KEGG mapping NPY MAP2K5 . ETV5 CADM2 PBEF1 GYS2 NUCB2 CAPN10 (LEPR, PRKCH, PACS1 and RMST (GWAS)) CNKSR2 SAA1

Infectious agents

  • Adenovirus 36 has been implicated in childhood obesity Atkinson et al, 2010
  • Dengue hemorrhagic fever has been associated with obesity in Thailand Pichainarong et al, 2006
  • The bifidobacterial numbers (microbiome) in faecal samples during infancy is lower in obese children, while Staphylococcus aureus presence is higher Kalliomaki et al, 2008
  • Absence of Helicobacter pylori infection, especially during childhood, may increase the risk of the subsequent development of obesity Wu et al, 2005
  • Higher levels of infections in childhood were associated with a low level of high density lipoprotein , higher level of triglycerides, plasma glucose, waist circumference, and obesity, but not hypertensionMargolis 2010
  • A higher number of bacteria in the oral microbiome has been associated with adolescent obesity: Campylobacter rectus and Neisseria mucosa were present in sixfold higher amounts among obese subjects Zeigler et al, 2012.

Autoimmunity

  • Anti tetanus Immunoglobulin G antibodies heve been reported to be lower in overweight children Eliakim et al, 2006
  • Antithyroid antibodies have been observed in some groups and some show ultrasound features of Hashimoto's thyroiditis, where thyroid destruction is a result of an auitoimmune process Radetti et al, 2008

Prenatal factors and Birth related

  • Breast feeding may lead to lower obesity Turck et al, 2005 Schack-Nielsen and Michaelsen 2007
  • High birth weight has been related to childhood obesity and diabetes Wei et al, 2007.
  • Antibiotics during the first 6 months of life increased the risk of overweight among children of normal weight mothers and decreased the risk of overweight among children of overweight mothers: An effect possibly related to the gut microbiome Ajslev et al, 2011.
  • Antibiotic use during the first 12 months of life has been associated with a small increase in BMI in boys aged 5 to 8 years Murphy et al, 2013
  • Higher maternal prenatal omega-3 polyunsaturated fatty acids are associated with lower rates of later childhood obesity Donahue et al, 2011
  • Early gut microbiota modulation with the probiotic Lactobacillus rhamnosus , in pregnant mothers may modify the growth pattern of the child and restrain excessive weight gain during the first years of life Luoto et al, 2010
  • Maternal diabetes is a risk factor for the development of obesity in childhood Temple et al, 2011
  • Maternal depression may affect childhood obesity Duarte et al, 2012
  • Adiposity at birth predicts overweight at the age of 5 years Winter et al, 2010.
  • Prolonged bottle feeding in infants has been linked to childhood obesity Gooze et al, 2011
  • Caesarian section may increase the likelihood of developing obesity in later life Goldani et al, 2011
  • First born status may increase the risk of developing obesity in later life Stettler et al, 2000
  • Antibiotics during the first 6 months of life increased the risk of overweight among children of normal weight mothers and a decreased the risk of overweight among children of overweight mothers (effects attributed to the microbiome ) Ajslef et al, 2011
  • A higher rate of growth during the first month after birth (peak weight velocity) was associated with obesity at 4 years old Mook-Kanamori et al, 2011
  • Prenatal gene methylation at birth (NOS3, RXRA) was associated with adiposity : RXRA but not NOS3 methylation was associated with lower maternal carbohydrate intake in early pregnancy Godfrey et al, 2011
  • Prenatal exposure to natural disasters increases risk for obesity in 5½-year-old children Dancause et al, 2012
  • Prenatal exposure to high magnetic fields has been associated with obesity Li et al, 2012
  • Maternal vitamin D deficiency in pregnancy has been linked to the development of adiposity in the offspring Crozier et al, 2012
    • Obese mothers transfer less 25-hydroxyvitamin D to their offspring during pregnancy Josefson et al, 2013
  • Polycyclic aromatic hydrocarbon exposure during pregnancy has been associated with obesity in the offspring Rundle et al, 2012,
  • Prenatal Dieldrin levels have shown a slight associationwith childhood obesity Cupul-Uicab et al, 2013
  • Tobacco smoke exposure before, during, and after pregnancy is a risk factor for the development of childhood overweight Raum et al, 2011.
  • Premature male children of mothers with pre-eclampsia are prone to obesity Washburn et al, 2013
  • DDT has been associated with obesity in boys and polychlorinated biphenyls and dichlorodiphenyldichloroethylene (DDE) in girls Valvi et al, 2012
Dietary factors
  • Aspartame has been linked with obesity RSS feed See toxins below
  • Fructose consumption has been linked with obesity RSS feed
  • Artificial sweeteners and obesity RSS feed
  • Supersweet sweetener database
  • Non-adherence to the mediterranean diet has been liked to childhood obesity in Greece (The GRECO study) Farajian et al, 2011
  • Proximity to fast food outlets predicts fatness in boys Chiang et al, 2011
  • :Intakes of protein, meat and fruit at age 18 months associate with measures of adiposity at age 8 years Garden et al, 2011
  • Overweight in Jamaican 15-19-year-olds is associated with increased consumption of sweetened beverages. High waist circumference in women is related to low consumption of fruits and vegetables Francis et al, 2009
  • Higher glycaemic load (carbohydrate content in diet) is associated with obesity in Japan Murakami et al, 2011
  • Childhood obesity is associated with excessive consumption of soft drinks, fast food, and excessive television watching Wen et al, 2010
  • Frequent consumption of sweets/candy and carbonated drinks relate to obesity in Saudi Arabia Amin et al, 2008
  • Lack of breastfeeding, high infantile energy intake (among formula or mixed-fed infants ) and high intake of sugar-sweetened beverages contribute to obesity development Moreno and Rodrigues, 2007.
  • Consumption of rice, bread, pasta, fast foods and fat/salty snacks was associated with childhood body mass index in Iran Kelishadi et al, 2003
  • Improvements in fitness from childhood to adolescence are associated with a lower risk of becoming overweight/obese in adolescence Ortega et al, 2011.
  • The factors with the greatest effect on obesity were family history of obesity: both parents (Odds ratio = 11.2), mother but not father (Odds ratio = 9.1), father but not mother (Odds ratio = 6.1), siblings Odds ratio = 2.7); and eating between meals (Odds ratio= 2.5) and consumption of sweets and soft drinks >2 times/week (Odds ratio = 2.0). The highest protection effect was found for five meals per day (Odds ratio = 0.5), the regular consumption of breakfast (Odds ratio = 0.5) and for eating fruit for dessert (Odds ratio = 0.6). Sedentary habits did not appear as important Zurriaga et al, 2011.
  • Children whose diet contains olive oil are less at risk for obesity Haro-Mora et al, 2011
  • Early gut microbiota modulation with probiotics may modify the growth pattern of the child by restraining excessive weight gain during the first years of life Luoto et al, 2010.
  • The use of antibiotics in infancy influences the risk of overweight in later childhood (microbiome related) Ajslev et al, 2011. Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Trasande et al, 2012
  • Childhood obesity is less of a problem in families who spent more time engaged with each other during the meal, expressed more positive communication, and considered mealtimes more important and meaningful Fiese et al, 2012

Epidemiology

  • Childhood obesity is associated with the father's body mass index, and mother's or child's dieting, or a rapid increase in body weight during the first year of life Vogels et al, 2006
  • Birthweight = 2.5 kg and = 4 kg, early introduction of solid foods and low physical activity were associated with obesity as were Maternal and grandmother's obesity, fewer children in the household, higher parental education, household income and the presence of familial obesity Saker et al, 2011
  • Short sleep duration was shown to be a risk factor for obesity in 7 year oldchildren Nixon et al, 2008
  • Tonsillectomy has been associated with obesity Jeyakumar et al, 2011
  • Higher rates of overweight and obesity have been observed in girls aged four to nine whose parents were single : Children in single-parent households watched more television, ate more fat and sugar and less fresh fruit and vegetables Byrne et al, 2011
  • Encouraging less sedentary behavior and higher levels of physical activity could alleviate the influence of risk alleles on the genetic predisposition to childhood obesity (noted for BDNF and MC4R) Xi et al, 2011 and for FTO Kilpeläinen et al, 2011
  • Childhood obesity has been related to standing posture Smith et al, 2011
  • Childhood sexual abuse has been associated with a higher risk of dyslipidemia and abdominal obesity van Reedt Dortland et al, 2011.
  • Deficiency of the essential metal zinc decreases adiposity in humans and rodent models, and deficiencies of chromium, copper, iron, and magnesium increases adiposity : Barium and thallium levels positively associated with obesity : Lead, cadmium, cobalt and cesium were negatively correlated with obesity Padilla et al, 2010
  • Adolescent participation in summer camps including regular physical activity reduces the subsequent risk of obesity Mahoney, 2011
  • Informal child care has been associated with childhood obesity Lin et al, 2011
  • Pesticides and disease database
  • improvements in fitness from childhood to adolescence are associated with a lower risk of becoming overweight/obese in adolescence Ortega et al, 2011.
  • The vicinity of healthy food outlets associates with a decrease in the likelihood of a child being overweight or obese Miller et al, 2013

Association with other diseases

  • Asthma among children and adolescents has been associated with obesity The association was stronger in nonatopic children than in atopic children Visness et al, 2010
  • Acanthosis nigricans (skin hyper pigmentation) has been associated wuth childhood obesity in Korea Chang et al, 2008
  • Juvenile psoriasis can be associated with increased rates of hyperlipidaemia, obesity, hypertension, diabetes mellitus, rheumatoid arthritis and Crohn disease Augustin et al, 2010
  • Eczema has been associated with lower risk of obesity in 6-7 year old girls, and 13-14 year old boys Violante et al, 2005
  • Childhood obesity can lead to the metabolic syndrome, atherosclerosis, dyslipidemia, hypertension and type 2 diabetes Halpern et al, 2010
    • The metabolic syndrome is prevalent in childhood obesity, particularly in pubertal patients Sangun et al, 2011
  • Hypertriglyceridemia is a consequence of childhood obesity de Ferranti et al, 2010
  • Nonalcoholic fatty liver disease can be a consequence of childhood obesity Barshop et al, 2009
  • Gallstones can be a consequence of childhood obesity Kratzer et al, 2010
  • Kidney stone risk may be related to obesity in youth Borysewicz-Sanczyk et al 2012
  • Childhood obesity increases the risk of obstructive sleep apnea syndrome Kohler et al, 2009
  • Maternal smoking during pregnancy and maternal and paternal heavy smoking increase the risk of childhood obesity and short stature Koshy et al, 2011
  • Childhood obesity and maternal smoking, increase the risk of developing Attention Deficit Hyperactivity Disorder Koshy et al, 2011
  • Obesity can be associated with bronchitis and with the use of antibiotics Wijka et al, 2010
  • Childhood obesity can lead to the cardiometabolic syndrome and increased cardiovascular risk in adulthood.Allcock et al, 2009
  • childhood obesity is associated with higher blood pressures and greater circulating cholesterol levels independently of physical activity McMurray et al, 1995
  • It can also lead to nonalcoholic liver disease type pathology Wiegand et al, 2010
  • Abdominal obesity in diabetic children is higher than in the general population Szadkowska et al, 2009
  • Studies in obese humans or animals show impaired immune function, decreased cytokine production, or response to antigen/mitogen stimulation, reduced macrophage , dendritic cell and natural killer cell function. This leads to increased susceptibility to infection including tuberculosis, influenza, Mycobacterium tuberculosis, coxsackievirus, Helicobacter pylori and the encephalomyocarditis virus Carlsson and Beck, 2010.
  • Chronic otitis media (ear inflammation with bacterial infection ) affects taste sensation and can contribute to obesity Medscape
  • Early menarche can be a consequence of childhood obesity Mumbi et al, 2011
  • Certain childhood cancers and particularly survivors of craniopharyngioma can be associated with childhood obesity Iughetti et al, 2011
  • Gastroesophageal reflux disease is associated with extreme childhood obesity Koebnick et al, 2011
  • Developmental coordination disorder has been associated with childhood obesity Wagner et al, 2011
  • Height and obesity during childhood was associated with increased risk of colorextal adenoma later in life in women Nimptsch et al, 2011
  • Childhood obesity has been associated with an increased risk of idiopathic intracranial hypertension Brara et al, 2012
  • Early life obesity may predispose to breast cancer in later life Sangaramoorthy et al, 2012
  • Association with atention deficit hyperactivity disorder Koshy et al, 2011
  • Childhood obesity may lead to increased morbidity from multiple scleros and clinically isolated syndrome, particularly in adolescent girls Langer-Gould et al, 2013.
  • Childhood-adolescence obesity has been reported as risk factor for adult depression Sanchez-Villegas et al, 2013.

Biochemistry

  • Blood pressure and fasting insulin and cholesterol concentrations are higher in obese children St Onge et al, 2003
  • Increased serum leptin, decreased adiponectin and resistin levels and reduced PON1 activity in obesity Seres et al, 2010
  • Serum VLDL, Triglyceride G, insulin, PAI-1 and TNFalpha levels were higher, and HDL and TGFbeta levels were lower in childhood obesity: Kinik et al, 2008
  • Increased Thyroid stimulating hormone levels have been noted in obese children Bhowmick et al, 2007
  • Increased endothelin 1 plasma levels have been noted in obese children Glowinska et al, 2004
  • Obese subjects with insulin resistance but without metabolic syndrome have higher serum C-reactive protein ( CRP ) fibrinogen, IL-6, and plasminogen activator inhibitor-1 serum levels Mauras et al, 2010
  • Obese children had higher levels of prostaglandin F-2 alpha and CRP, fasting insulin levels and HOMA index compared to healthy subjects: They also had increased carotid intima thickness, a marker of atherosclerosis Giannini et al, 2008 (The HOMA-IR value is the product of the patient's blood glucose and insulin serum levels after fasting, divided by a constant value) Plasma pro brain natriuretic peptide concentrations are lower in male childhood obesity , compared to normal normotensive controls but higher in the obese hypertensive than the obese normotensive group Pervanidou et al, 2010.
  • Nonesterified fatty acid concentrations are elevated in obese children, primarily as a result of increases in myristate, palmitate, and oleate Sabin et al, 2007
  • Increased levels of blood polyamines (putrescine, spermidine, and particularly spermine) in childood obesity Codoñer-Franch et al, 2011
  • Childhood obesity is associated with high circulating Plasminogen activator inhibitor-1 (PAI-1) levels Mantovani et al, 2011
  • High circulating levels of thyroid-stimulating hormone Stichel et al, 2000
  • Higher CRP levels associated with higher body mass and overweight/obesity risk in a large population of European children Nappo et al, 2013.

Toxins

  • Aspartame High concentrations of aspartame in weanling mice can induce neuronal lesions in the hypothalamic arcuate nuclei: water-restricted weanling mice lose their ability to regulate drinking behavior, and consume high aspartame concentrations whose osmolarity or sweetness would normally be aversive Takasaki et al, 1981 ( The arcuate nucleus controls appetite )
  • A rise in obesity coincides with an increased use of non-caloric artificial sweeteners, such as aspartame Yang, 2010
  • Aspartame can induce spikes in blood levels of aspartate Aspartame metabolome
  • Long term consumption of aspartame leads to hepatic injury and alterations in liver antioxidant glutahione status Abhilash et al, 2011.
  • Excessive intake of caloric sports drinks can substantially increase the risk for overweight or obesity in children and adolescents . Pediatrics 2011 COMMITTEE ON NUTRITION AND THE COUNCIL ON SPORTS MEDICINE AND FITNESS
  • The addition of artificial sweeteners to a yeast extract, peptone, and tryptone medium without supplemented sugar increased the growth rate and final biomass of Lactobacillus delbrueckii subsp. bulgaricus Manca de Nadra et al, 2007
  • Aspartame and other artificial sweeteners activate TRPV1 Riera et al, 2007
  • Monosodium glutamate destroys neurons of the arcuate hypothalamic nucleus in rats and produces hyperinsulinemic and hypophagic obesity Scallett and Olney, 1986.
  • Organochlorine chemicals and peroxisome proliferator-activated receptor agonists have ben identified as risk factors La Merrill and Birnbaum 2011
  • Chronic lead exposure in childhood may result in obesity that persists into adulthood Kim et al, 1995
  • Urinary bisphenol A concentrations have been associated with childhood obesity Trasande et al, 2012. Li et al, 2013

 

 

 

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