Abstract Childhood obesity is associated with type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). Recent studies have found associations between vitamin D deficiency (VDD), insulin resistance (IR), NAFLD among overweight children. To further explore mechanisms mediating these effects, we fed young (age 25 days) Sprague-Dawley rats a low-fat diet (LFD) alone or depletion (LFD+VDD). A second group of was exposed to Westernized (WD: high-fat/high-fructose corn syrup) that...

Irisin is a recently identified myokine affecting metabolic and glucose homeostasis. However, the role of irisin in obesity its consequences are controversial, data children scarce. To study relationships between irisin, insulin resistance, puberty before after weight loss obese with without impaired tolerance. One-year follow-up participating lifestyle intervention. Primary care. Forty 20 normal-weight similar age, gender, pubertal stage. A 1-year outpatient intervention program based on...

Low-serum concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with insulin resistance in adults. Less data available pediatric populations. Serum 25(OH)D serum were assessed 125 obese and 31 nonobese children (age 11.9 ± 2.7 y, range 6-16 49% male) living Bonn, Germany. The relationship between 25(OH)D, measured by liquid chromatography-tandem mass spectrometry, measures sensitivity adipokines adiponectin resistin analyzed. Seventy-six % subjects deficient (<20 ng/mL). Higher...

Obesity and adiponectin depletion have been associated with the occurrence of nonalcoholic fatty liver disease (NAFLD). The goal this study was to identify relationship between weight gain, signaling, development steatohepatitis (NASH) in an obese, diabetic mouse model. Leptin-receptor deficient (Lepr(db/db) ) C57BL/6 mice were administered a diet high unsaturated fat (HF) (61%) or normal chow for 5 10 weeks. Liver histology evaluated using steatosis, inflammation, ballooning scores. Serum,...

Objective Excessive weight gain frequently occurs in patients with hypothalamic tumors and lesions leading to obesity (HO). Methods Digital brain magnetic resonance imaging (MRI) clinical outcomes were studied retrospectively a single center, including 45 children postoperative the sellar region (41 craniopharyngiomas, 4 Rathke's cleft cysts), ∼5 years post‐surgery, mean age 13.9 years. Four standard sections covering areas critical energy homeostasis used assess calculate lesion score...

To evaluate the efficacy, safety and tolerability of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with hypothalamic obesity (HO).A two-arm, randomized, multicentre, double-blind, placebo-controlled trial was conducted 10- to 25-year-olds injury following intracranial tumour HO. Participants were randomized once-weekly subcutaneous injections GLP-1 RA exenatide 2 mg (ExQW) or placebo for 36 weeks. The primary efficacy endpoint 36-week % change body mass index (BMI)....

Pediatric cohorts of central diabetes insipidus (CDI) have shown varying prevalences for the different causes CDI, including idiopathic. The objective study was to determine CDI at a pediatric tertiary care center and characterize their clinical outcomes. All patients with Seattle Children's Hospital were identified retrospectively analyzed. From 2000 2013, 147 encountered (mean age 7 y diagnosis, mean follow-up 6.2 y). grouped, anterior pituitary hormone deficiencies (APHDs), presence...

Abstract Mechanisms underlying long-term sustained weight loss and glycemic normalization after obesity surgery include changes in gut hormone levels, including glucagon-like peptide 1 (GLP-1) YY (PYY). We demonstrate that two biased agonists (GEP44 GEP12) of the GLP-1, neuropeptide Y1, Y2 receptors (GLP-1R, Y1-R, Y2-R, respectively) elicit Y1-R antagonist-controlled, GLP-1R-dependent stimulation insulin secretion both rat human pancreatic islets, thus revealing counteracting effects GLP-1R...

We recently reported that a chimeric peptide (GEP44) targeting the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- Y2-receptors decreased body weight (BW), energy intake core temperature in diet-induced obese (DIO) male female mice. Given GEP44 was found to reduce (surrogate measure of expenditure (EE)) DIO mice, we hypothesized would EE high fat diet (HFD)-fed rats. To test this, rats were maintained on HFD for at least 4 months elicit prior undergoing sequential 2-day...

We recently reported that a chimeric peptide (GEP44) targeting the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- Y2- receptors decreased body weight (BW), energy intake, core temperature in diet-induced obese (DIO) male female mice. In current study, we tested hypothesis strong reduction response to GEP44 is partially related stimulation of expenditure (EE). To test this, rats were maintained on high fat diet (HFD) for at least 4 months elicit DIO prior undergoing sequential...

For patients with a craniopharyngioma (CP), treatment of hypothalamic obesity (HO) and hyperphagia following resection and/or radiotherapy is extremely difficult few reports have been published on potential drug therapies. Psychomotor stimulant methylphenidate (MPH) has reported to inhibit food intake (FI). In this paper, we report reduction body mass index (BMI) appetite in an adolescent CP patient suffering from HO. We then tested the ability MPH attenuate FI weight (BW) gain rat model...

There is a critical unmet need for therapeutics to treat the epidemic of comorbidities associated with obesity and type 2 diabetes, ideally devoid nausea/emesis. This study developed monomeric peptide agonists glucagon-like 1 receptor (GLP-1R) neuropeptide Y2 (Y2-R) based on exendin-4 (Ex-4) PYY3–36. A novel peptide, GEP44, was obtained via in vitro screens, insulin secretion islets, stability assays, vivo rat shrew studies glucoregulation, weight loss, nausea, emesis. GEP44 lean...

Dopamine receptors are involved in midbrain reward circuit activation. Polymorphisms two dopamine receptor genes, DRD2 and DRD4, have been associated with altered perception of food weight gain. The objective this study was to determine whether the same risk alleles were overweight/obesity lower reduction overweight after a 1-year lifestyle intervention.In longitudinal association polymorphisms (rs18000497, allele: T, formerly A1 allele at TaqI polymorphism) DRD4 (variable number tandem...

To evaluate whether neuroimaging-delineated regions of hypothalamic injury are associated with a differential treatment response to glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients obesity (HO).We performed prespecified secondary analysis randomized, multicentre, double-blind, placebo-controlled trial people aged 10-25 years and HO randomized the GLP-1RA exenatide once-weekly (ExQW) or placebo for 36 weeks. Subjects underwent MRI prior enrolment degree damage was assessed using...

We recently reported that a novel chimeric peptide (GEP44) targeting both the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- Y2 (Y1R Y2R) reduced energy intake body weight (BW) in diet-induced obese (DIO) rats. hypothesized GEP44 reduces BW primarily through GLP-1R dependent mechanism. To test this hypothesis, GLP-1R+/+ mice null (GLP-1R-/-) were fed high fat diet for 4 months to elicit obesity prior undergoing sequential 3-day vehicle period, drug treatment (5, 10, 20 or 50...

Challenges to peptide-based therapies include rapid clearance, ready degradation by hydrolysis/proteolysis, and poor intestinal uptake and/or a need for blood brain barrier transport. This work evaluates the efficacy of conjugation vitamin B12 (B12) on sc administered peptide tyrosine (PYY)3–36 function. In current experiments, B12-PYY3–36 conjugate was tested against native PYY3–36, an inactive B12-PYYC36 (null control) in vitro vivo. experiments demonstrated similar agonism neuropeptide Y2...

Abstract Context Behavioral studies suggest that responses to food consumption are altered in children with obesity (OB). Objective To test central nervous system and peripheral hormone response by functional MRI satiety-regulating levels before after a meal. Design Setting Cross-sectional study comparing OB of healthy weight (HW) recruited from across the Puget Sound region Washington. Participants Children (9 11 years old; OB, n = 54; HW, 22), matched for age sex. Intervention Outcome...

Hypothalamic obesity (HO) is a major and unsolved problem in patients with medial hypothalamic lesions associated hyperinsulinemia hyperleptinemia. The purpose of this study was to create rodent model that mimics metabolic changes HO for use therapeutic testing. Female Sprague-Dawley rats were used test the individual combined effects two types lesions: arcuate nucleus (ARC) by injection monosodium glutamate at neonatal age, ventromedial (VMN) passing an anodal current through electrode...

Hypothalamic lesions or deficient melanocortin (MC) signaling via MC4 receptor (MC4r) mutations often lead to hyperphagia and severe treatment-resistant obesity. We tested the methionine aminopeptidase 2-inhibitor beloranib (ZGN-440) in 2 male rat models of obesity, one modeling hypothalamic obesity with a combined medial lesion (CMHL) other monogenic form MC4r (MC4r knockout [MC4rKO]). In CMHL rats (age 3 months), postsurgery excess weight gain was significantly inhibited (ZGN-440, 0.2 ±...

The influences of obesity, glucose metabolism, gender, and puberty on betatrophin levels the longitudinal relationships between weight loss, metabolic changes have not yet been studied in childhood.Cross-sectional analysis status (standard deviation score-body mass index (SDS-BMI)), homeostasis model assessment insulin resistance (HOMA-IR), pubertal stage were evaluated 69 obese children (51% female, age 11.9 ± 2.0 years) participating lifestyle intervention over a 1-year period. An oral...