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Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

Morimoto-Kobayashi Y, Ohara K, Takahashi C, Kitao S, Wang G, Taniguchi Y, Katayama M, Nagai K - PLoS ONE (2015)

Bottom Line: Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents.MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation.We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels.

View Article: PubMed Central - PubMed

Affiliation: Research Laboratories for Health Science & Food Technologies, KIRIN Company, Ltd., Yokohama, Kanagawa, Japan.

ABSTRACT
Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or beverages to counteract the accumulation of body fat.

No MeSH data available.


Related in: MedlinePlus

Measurement of mRNA expression levels and Immuno-blot analysis in the interscapular BAT of mice fed HFD supplemented with MHB.(A) mRNA expression levels in BAT. mRNA expression levels were normalized to the expression level of GAPDH as a reference. (B) Immuno-blot analysis of UCP1 in BAT mitochondria. Representative immuno-blots are shown on the histogram. Representative signals shown are from the same immuno-blot membrane. UCP1 protein level was normalized to the level of UQCRC1 protein as a reference. Data are presented as means ± SEM. n = 12 mice/group. *P < 0.05, **P < 0.01 (by unpaired Student’s t-test).
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pone.0131042.g002: Measurement of mRNA expression levels and Immuno-blot analysis in the interscapular BAT of mice fed HFD supplemented with MHB.(A) mRNA expression levels in BAT. mRNA expression levels were normalized to the expression level of GAPDH as a reference. (B) Immuno-blot analysis of UCP1 in BAT mitochondria. Representative immuno-blots are shown on the histogram. Representative signals shown are from the same immuno-blot membrane. UCP1 protein level was normalized to the level of UQCRC1 protein as a reference. Data are presented as means ± SEM. n = 12 mice/group. *P < 0.05, **P < 0.01 (by unpaired Student’s t-test).

Mentions: To elucidate the underlying mechanisms of the effects of MHB, quantitative RT-PCR was carried out using tissues from mice after 9 wk feeding of MHB. Supplementation with MHB significantly increased the mRNA levels of PGC-1α, UCP1, CPT1β and ACO genes by 1.6-fold, 1.2-fold, 1.3-fold, 1.2-fold in BAT, respectively (Fig 2A). The mRNA levels of PRDM16 and PPARγ were also significantly increased by feeding MHB. There was also a concomitant increase in the UCP1 protein level in BAT mitochondria isolated from MHB fed mice (1.3-fold, P < 0.01) (Fig 2B). Although the mRNA levels of FAS in the liver and ACC1 in the gastrocnemius muscle were significantly increased in the MHB-fed mice, no inclusive changes of gene expression were observed in the gastrocnemius muscle and liver between the groups (S4 Fig). These results indicate that MHB induces an increase in the mRNA levels of genes related to thermogenesis and fatty acid oxidation in BAT.


Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

Morimoto-Kobayashi Y, Ohara K, Takahashi C, Kitao S, Wang G, Taniguchi Y, Katayama M, Nagai K - PLoS ONE (2015)

Measurement of mRNA expression levels and Immuno-blot analysis in the interscapular BAT of mice fed HFD supplemented with MHB.(A) mRNA expression levels in BAT. mRNA expression levels were normalized to the expression level of GAPDH as a reference. (B) Immuno-blot analysis of UCP1 in BAT mitochondria. Representative immuno-blots are shown on the histogram. Representative signals shown are from the same immuno-blot membrane. UCP1 protein level was normalized to the level of UQCRC1 protein as a reference. Data are presented as means ± SEM. n = 12 mice/group. *P < 0.05, **P < 0.01 (by unpaired Student’s t-test).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4476742&req=5

pone.0131042.g002: Measurement of mRNA expression levels and Immuno-blot analysis in the interscapular BAT of mice fed HFD supplemented with MHB.(A) mRNA expression levels in BAT. mRNA expression levels were normalized to the expression level of GAPDH as a reference. (B) Immuno-blot analysis of UCP1 in BAT mitochondria. Representative immuno-blots are shown on the histogram. Representative signals shown are from the same immuno-blot membrane. UCP1 protein level was normalized to the level of UQCRC1 protein as a reference. Data are presented as means ± SEM. n = 12 mice/group. *P < 0.05, **P < 0.01 (by unpaired Student’s t-test).
Mentions: To elucidate the underlying mechanisms of the effects of MHB, quantitative RT-PCR was carried out using tissues from mice after 9 wk feeding of MHB. Supplementation with MHB significantly increased the mRNA levels of PGC-1α, UCP1, CPT1β and ACO genes by 1.6-fold, 1.2-fold, 1.3-fold, 1.2-fold in BAT, respectively (Fig 2A). The mRNA levels of PRDM16 and PPARγ were also significantly increased by feeding MHB. There was also a concomitant increase in the UCP1 protein level in BAT mitochondria isolated from MHB fed mice (1.3-fold, P < 0.01) (Fig 2B). Although the mRNA levels of FAS in the liver and ACC1 in the gastrocnemius muscle were significantly increased in the MHB-fed mice, no inclusive changes of gene expression were observed in the gastrocnemius muscle and liver between the groups (S4 Fig). These results indicate that MHB induces an increase in the mRNA levels of genes related to thermogenesis and fatty acid oxidation in BAT.

Bottom Line: Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents.MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation.We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels.

View Article: PubMed Central - PubMed

Affiliation: Research Laboratories for Health Science & Food Technologies, KIRIN Company, Ltd., Yokohama, Kanagawa, Japan.

ABSTRACT
Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or beverages to counteract the accumulation of body fat.

No MeSH data available.


Related in: MedlinePlus