The −3826 A→G Variant of the Uncoupling Protein-1 Gene Diminishes Postprandial Thermogenesis after a High Fat Meal in Healthy Boys

Nagai, Narumi; Sakane, Naoki; Ueno, Linda Massako; Hamada, Taku; Moritani, Toshio

doi:10.1210/jc.2003-030672

Cited by 78 publications

(51 citation statements)

References 18 publications

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“…Accordingly, diminished REE observed in G-allele carriers may be caused primarily by attenuated UCP1-linked thermogenesis. This finding appears to be inconsistent with our previous pediatric studies 10,11 that there were no significant effects of this polymorphism on baseline REE in healthy children. This discrepancy may be explained by the difference in the age of the subjects; that is, they were 8-11 (Nagai et al 10 ) or 6-10 (Nagai et al 11 ) years old in the previous studies, being younger than those in the present study (20-22 years old).…”

Section: Discussioncontrasting

confidence: 99%

“…10,11 After the phenol-extraction procedure, 0.2-2 mg of DNA was obtained per subject. The -3826A/G polymorphic region of UCP1 (rs1800592) was amplified using the PCR with a sense primer (5 0 -TTT GTG CAG CGA TTT CTG ATT GAC-3 0 ), an anti-sense primer (5 0 -AGG AGT GGC AGC AAG TTC TGA ATG-3 0 ) and a primer labeled at the 5 0 end with Texas red (5 0 -AAA TGC ACT CGA TCA AAC TGT-3 0 ).…”

Section: Genetic Analysismentioning

confidence: 99%

“…7 Accordingly, genetic polymorphism, such as the -3826 A/G single nucleotide polymorphism in the promoter in exon 2 of UCP1, has been reported to be associated with obesity phenotypes 8 causing reduced mRNA expression. 9 We previously reported that healthy children with the G/G genotype had a lower capacity for thermogenesis in response to a high-fat meal 10 and acute cold exposure. 11 These findings of reduced UCP1-linked thermogenesis in children with the G/G genotype support the metabolic significance of human BAT, at least in children.…”

Section: Introductionmentioning

confidence: 99%

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UCP1 genetic polymorphism (–3826 A/G) diminishes resting energy expenditure and thermoregulatory sympathetic nervous system activity in young females

et al. 2010

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Background: Recent findings regarding the existence of functional brown adipose tissue (BAT) in adult humans suggest a physiological role of BAT and uncoupling protein 1 (UCP1)-linked thermogenesis in energy balance. Objective: To investigate whether UCP1 polymorphism was associated with resting energy expenditure (REE) and thermoregulatory sympathetic nervous system (SNS) activity in humans. Methods: A total of 82 healthy females (20-22 years) were genotyped for the -3826 A/G polymorphism of the UCP1 gene using a fluorescent allele-specific DNA primer assay system. REE was measured by indirect calorimetry. The thermoregulatory SNS activity was assessed by heart rate variability power spectral analysis according to our previously reported method. Each subject was studied in the morning, after an overnight fast. Nutritional values were calculated on the basis of 2-day food records.

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Section: Discussioncontrasting

confidence: 99%

Section: Genetic Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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UCP1 genetic polymorphism (–3826 A/G) diminishes resting energy expenditure and thermoregulatory sympathetic nervous system activity in young females

et al. 2010

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“…29 As the sympathetic branch of the autonomic system particularly contributes to coordinating energy homeostasis, any alteration in sympathetic nervous system is widely assumed to promote onset and development of obesity. 14,30 Nagai et al 30 showed that the complete autonomic blockade evaluated by means of PSA of HRV significantly reduced the energy expenditure in humans. In addition, Heinonen et al 1 found that the Glu 9 /Glu 9 genotype was associated with reduced basal metabolic rate in obese Finns population.…”

Section: Discussionmentioning

confidence: 99%

α2B-Adrenergic receptor deletion polymorphism and cardiac autonomic nervous system responses to exercise in obese women

et al. 2005

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Objective: To investigate the association of short form (Glu 9 /Glu 9 ) of the 12Glu9 deletion polymorphism of the a 2B -adrenergic receptor (a 2B -AR) gene polymorphism with the cardiac autonomic responsiveness during sustained isometric handgrip exercise. Design: Cross-sectional clinical study. Subjects: In all, 97 normotensive obese women (body mass index (BMI) ¼ 33.2 kg/m 2 ). Of these, 78 (80.41%) were genotyped as Glu 12 /Glu 12 , 13 (13.40%) as Glu 12 /Glu 9 and six (6.19%) as Glu 9 /Glu 9 form. Measurements: The sympathovagal balance was assessed by means of power spectral analysis of heart rate variability at rest and during sustained isometric handgrip exercise at 30% of maximal voluntary handgrip contraction for 3 min. Two spectral components were analysed: low-frequency component reflecting sympathetic efferent activity and high-frequency power (HFnu) reflecting parasympathetic modulation. In addition, a normalized low-frequency power (LFnu) and HFnu were analysed. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis. Results: There were no differences in baseline measurements among groups. The absolute level of LFnu throughout handgrip exercise was significantly lower in Glu 9 /Glu 9 subjects compared with other genotypes, while the decline of absolute HFnu was significantly smaller compared with Glu 12 /Glu 12 genotype. Conclusion: These findings suggest that 12Glu9 deletion polymorphism of the a 2B -AR gene (Glu 9 /Glu 9 genotype) might result in reduced autonomic responsiveness by altering cardiac sympathetic and vagal function during sustained handgrip exercise in normotensive obese women.

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“…In small mammals, its role in sympathetic control of thermoregulatory thermogenesis is well established, and its role in the control of DIT seems to be intimately linked, and secondary, to its role in thermal regulation. In humans, however, the notion that UCP1 is involved in DIT has been largely abandoned, although recent findings that children with UCP1 polymorphism (GG allele carriers) have lowered postprandial thermogenesis in response to a high-fat meal [94], raises the possibility that such UCP1-linked thermogenesis may have relevance for childhood obesity.…”

Section: Is There a Role For Uncoupling Proteins In Fat Metabolism Anmentioning

confidence: 99%

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

Dulloo

Seydoux

Jacquet

2004

Physiology & Behavior

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After decades of controversies about the quantitative importance of autoregulatory adjustments in energy expenditure in weight regulation, there is now increasing recognition that even subtle variations in thermogenesis could, in dynamic systems and over the long term, be important in determining weight maintenance in some and obesity in others. The main challenge nowadays is to provide a mechanistic explanation for the role of adaptive thermogenesis in attenuating and correcting deviations of body weight and body composition, and in the identification of molecular mechanisms that constitute its effector systems. This workshop paper reconsiders what constitutes adaptive changes in thermogenesis and reassesses the role of the sympathetic nervous system (SNS) and uncoupling proteins (UCP1, UCP2, UCP3, UCP5/BMCP1) as the efferent and effector components of the classical one-control system for adaptive thermogenesis and fat oxidation. It then reviews the evidence suggesting that there are in fact two distinct control systems for adaptive thermogenesis, the biological significance of which is to satisfy-in a lifestyle of famine-and-feast-the needs to suppress thermogenesis for energy conservation during weight loss and weight recovery even under environmental stresses (e.g., cold, infection, nutrient imbalance) when sympathetic activation of thermogenesis has equally important survival value.Keywords: Obesity; Diabetes; Cachexia; Catecholamines; UCP Resistance to obesity in an obesigenic environmentOne of the greatest challenges towards understanding the aetiology of human obesity is to explain how in environments that promote overeating of high-fat foods and discourage physical activity, there is always a section of the population who, apparently without conscious effort, do not become obese. How do they resist obesity? How is constancy of body weight achieved over decades in these individuals? In addressing the issue of human susceptibility to leanness and fatness, there are three cardinal features of body weight regulation that need to be underlined: (i) Humans cannot escape the laws of thermodynamics.Whatever theory is put forward to explain body weight and body composition regulation, it is undeniable that changes in body energy stores (and ultimately body weight) cannot occur unless there is a difference between energy intake and energy expenditure. (ii) Subtle perturbations in energy balance can lead to obesity. To put it another way, long-term constancy of body weight can only be achieved if the matching between energy intake and energy expenditure is extremely precise, since an error of only 1% between input and output of energy, if persistent, will lead to a gain or loss of 1 kg per year or some 40 kg between the age of 20 to 60 years. Yet, a difference of 5% between energy intake and energy expenditure is hardly measurable with available techniques. (iii) Body weight is a fluctuating and oscillatory phenomenon. Even in individuals that maintain a relatively stable lean body weight over decades, the...

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The −3826 A→G Variant of the Uncoupling Protein-1 Gene Diminishes Postprandial Thermogenesis after a High Fat Meal in Healthy Boys

Cited by 78 publications

References 18 publications

UCP1 genetic polymorphism (–3826 A/G) diminishes resting energy expenditure and thermoregulatory sympathetic nervous system activity in young females

UCP1 genetic polymorphism (–3826 A/G) diminishes resting energy expenditure and thermoregulatory sympathetic nervous system activity in young females

α2B-Adrenergic receptor deletion polymorphism and cardiac autonomic nervous system responses to exercise in obese women

Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

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