Dataset Information

A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity.

ABSTRACT:

Context

Children with obesity have low spontaneous growth hormone (GH) secretion. High circulating free fatty acid (FFA) concentration is believed to inhibit GH secretion in those with obesity. In adults, lipolytic inhibition with niacin lowers FFA and increases GH, but there are no prior studies in children with obesity.

Objective

The objective of the study was to determine the dose and frequency of niacin administration required to lower FFA and stimulate GH in children with obesity.

Design

Dose-finding study of nondiabetic children ages 6-12 years with body mass index (BMI) ≥ 95th percentile given niacin 250 mg q2h × 3 doses (n = 2), 500 mg q2h × 3 doses (n = 5) or 500 mg q1h × 4 doses (n = 5).

Participants

Eight boys and four girls (age 9.7 ± 1.8 years; BMI 26.4 ± 3.1 kg m^-2 ; BMIz 2.2 ± .25) were studied.

Main outcome

Percentage of serum FFA values that were below 0.2 mEq L^-1 . GH, insulin and glucose were also measured serially.

Results

FFA decreased as the dose and frequency of niacin increased (p = .01). Niacin 500 mg q1h 4 doses suppressed FFA < 0.2 mEq L^-1 and significantly increased GH (p = .04). Adverse effects were flushing/warmth (100%), tingling (60%) and GI complaints (20-40%).

Conclusions

Niacin 500 mg q1h significantly lowered serum FFA and increased GH. These pilot data suggest that high FFA is an important suppressor of GH secretion in children with obesity.

SUBMITTER: Galescu OA

PROVIDER: S-EPMC5360541 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity.

Galescu O A OA Crocker M K MK Altschul A M AM Marwitz S E SE Brady S M SM Yanovski J A JA

Pediatric obesity 20160921 1

<h4>Context</h4>Children with obesity have low spontaneous growth hormone (GH) secretion. High circulating free fatty acid (FFA) concentration is believed to inhibit GH secretion in those with obesity. In adults, lipolytic inhibition with niacin lowers FFA and increases GH, but there are no prior studies in children with obesity.<h4>Objective</h4>The objective of the study was to determine the dose and frequency of niacin administration required to lower FFA and stimulate GH in children with obe ...[more]

PMID: 27654882

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Project description:ObjectiveMaintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits somatostatin secretion. However, the contribution of individual islet cell types (α, β, and δ cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. As gpr120 mRNA is enriched in somatostatin-secreting δ cells, we hypothesized that GPR120 activation stimulates insulin and glucagon secretion via inhibition of somatostatin release.MethodsGlucose tolerance tests were performed in mice after administration of selective GPR120 agonist Compound A. Insulin, glucagon, and somatostatin secretion were measured in static incubations of isolated mouse islets in response to endogenous (ω-3 polyunsaturated fatty acids) and/or pharmacological (Compound A and AZ-13581837) GPR120 agonists. The effect of Compound A on hormone secretion was tested further in islets isolated from mice with global or somatostatin cell-specific knock-out of gpr120. Gpr120 expression was assessed in pancreatic sections by RNA in situ hybridization. Cyclic AMP (cAMP) and calcium dynamics in response to pharmacological GPR120 agonists were measured specifically in α, β, and δ cells in intact islets using cAMPER and GCaMP6 reporter mice, respectively.ResultsAcute exposure to Compound A increased glucose tolerance, circulating insulin, and glucagon levels in vivo. Endogenous and/or pharmacological GPR120 agonists reduced somatostatin secretion in isolated islets and concomitantly demonstrated dose-dependent potentiation of glucose-stimulated insulin secretion and arginine-stimulated glucagon secretion. Gpr120 was enriched in δ cells. Pharmacological GPR120 agonists reduced cAMP and calcium levels in δ cells but increased these signals in α and β cells. Compound A-mediated inhibition of somatostatin secretion was insensitive to pertussis toxin. The effect of Compound A on hormone secretion was completely absent in islets from mice with either global or somatostatin cell-specific deletion of gpr120 and partially reduced upon blockade of somatostatin receptor signaling by cyclosomatostatin.ConclusionsInhibitory GPR120 signaling in δ cells contributes to both insulin and glucagon secretion in part by mitigating somatostatin release.

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Dataset Information

A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity.

Context

Objective

Design

Participants

Main outcome

Results

Conclusions

Publications

A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity.

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