Resveratrol Induces Fat Browning, Weight Loss in Mice
Resveratrol Induces Fat Browning, Weight Loss in Mice
The polyphenol resveratrol appears to induce the browning of white fat by activating AMPK alpha 1.
Salynn Boyles
Contributing Writer
The polyphenol resveratrol may help protect against obesity and related metabolic diseases by promoting the browning of white adipose tissue (WAT), studies in mice suggest.
Resveratrol appeared to induce brown-like adipose formation in inguinal WAT by increasing the expression of genes specific to brown adipocytes and stimulating fatty acid oxidation, researcher Min Du, PhD, of Washington State University, Pullman, Washington, and colleagues wrote in the International Journal of Obesity.
Female mice fed a high-fat diet supplemented with resveratrol were found to be 40% less likely to develop diet-induced obesity than control mice whose diets were not supplemented with the antioxidant compound.
Recent studies in mice suggest that the natural polyphenol inhibits white fat formation to reduce adiposity, but the research is the first to suggest that polyphenols may have a role in the browning of adipose tissue, Du told MedPage Today.
"We know that polyphenolic compounds enhance lipid oxidation, but we have not known how," he said. "That is what led us to the hypothesis that these compounds induce the conversion of white to brown fat and enhance fat burning."
Resveratrol Is Widely Studied Polyphenol
Abundant in red wine, berries, dark chocolate, and nuts, resveratrol had a widely publicized moment a few years back when it was featured on "60 Minutes," "Oprah," and in countless print articles as a potential miracle anti-aging super-compound, based on studies in mice.
More recent research, including a 2014 NIH study of older people in Italy, suggests that resveratrol has little impact on longevity in humans.
The compound has been shown in numerous animal studies to protect against high-fat-diet-induced obesity and even metabolic injury associated with a high fat/sugar diet.
"We used resveratrol in our research because it has been studied extensively for the last 2 decades," Du said. "But we believe that total polyphenol content of foods is more important. Our research supports the idea that a diet rich in polyphenols enhances fat burning."
Resveratrol Promoted Fat Browning in In Vitro Studies
When the researchers studied the effects of resveratrol on brown adipogenic differentiation of inguinal WAT (iWAT) stromal vascular cells (SVCs), they found that higher concentrations (20 to 40 micrometers) of the polyphenol significantly (P<0.01) inhibited lipid accumulation in the differentiated iWAT SVCs. It also suppressed the expression of adipogenic markers PPAR-gamma and aP2. At concentrations of ≤10 micrometers, which is closer to plasma concentrations, resveratrol had no effect on lipid accumulation.
Resveratrol was found to significantly increase mRNA and/or protein expression of brown adipocyte markers, including uncoupling protein 1 (UCP1), PR domain-containing 16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty acids protein 3, peroxisome proliferator-activated receptor-gamma coactivators 1-alpha, cytochrome c, and pyruvate dehydrogenase in differentiated iWAT SVCs.
These findings suggest that resveratrol induces brown-like adipocyte formation in vitro, the researchers wrote.
Simultaneously, resveratrol enhanced AMP-activated protein kinase alpha 1 phosphorylation and differentiated SVC oxygen consumption.
AMPK alpha 1 Critical Mediator of Action
"Such changes were absent in cells lacking AMPK alpha 1, showing that AMPK alpha 1 is a critical mediator of resveratrol action," the researchers wrote.
When the researchers fed 5-month-old CD1 female mice a high-fat diet with or without 0.1% of resveratrol, they found that resveratrol feeding resulted in significant decreases in body weight gain compared with the control diet when challenged with a high-fat diet.
"Our findings confirmed the body fat-lowering effects of resveratrol, which have been reported in both animals and humans," the researchers wrote. "We found that resveratrol resulted in decreased adipocyte size in WAT, which is in agreement with a recent report in humans. More importantly, we observed brown-like adipocytes, with an appearance of multiocular lipid droplets, in iWAT, which has not been observed before."
Taken as a whole, the findings suggest that polyphenols like resveratrol enhance the oxidation and thermogenesis of white fat.
"Our results demonstrated that resveratrol induces the browning of mouse iWAT by promoting the expression of brown adipocyte selective genes through the activation of AMPK alpha 1," the researchers wrote.
The research was funded by the National Institutes of Health, the Natural Science Foundation of China, the Muscular Dystrophy Association, and the National Science Foundation.
The researchers declared no relevant relationships with industry.
Resveratrol Induces Fat Browning, Weight Loss in Mice
The polyphenol resveratrol appears to induce the browning of white fat by activating AMPK alpha 1.
Salynn Boyles
Contributing Writer
The polyphenol resveratrol may help protect against obesity and related metabolic diseases by promoting the browning of white adipose tissue (WAT), studies in mice suggest.
Resveratrol appeared to induce brown-like adipose formation in inguinal WAT by increasing the expression of genes specific to brown adipocytes and stimulating fatty acid oxidation, researcher Min Du, PhD, of Washington State University, Pullman, Washington, and colleagues wrote in the International Journal of Obesity.
Female mice fed a high-fat diet supplemented with resveratrol were found to be 40% less likely to develop diet-induced obesity than control mice whose diets were not supplemented with the antioxidant compound.
Recent studies in mice suggest that the natural polyphenol inhibits white fat formation to reduce adiposity, but the research is the first to suggest that polyphenols may have a role in the browning of adipose tissue, Du told MedPage Today.
"We know that polyphenolic compounds enhance lipid oxidation, but we have not known how," he said. "That is what led us to the hypothesis that these compounds induce the conversion of white to brown fat and enhance fat burning."
Resveratrol Is Widely Studied Polyphenol
Abundant in red wine, berries, dark chocolate, and nuts, resveratrol had a widely publicized moment a few years back when it was featured on "60 Minutes," "Oprah," and in countless print articles as a potential miracle anti-aging super-compound, based on studies in mice.
More recent research, including a 2014 NIH study of older people in Italy, suggests that resveratrol has little impact on longevity in humans.
The compound has been shown in numerous animal studies to protect against high-fat-diet-induced obesity and even metabolic injury associated with a high fat/sugar diet.
"We used resveratrol in our research because it has been studied extensively for the last 2 decades," Du said. "But we believe that total polyphenol content of foods is more important. Our research supports the idea that a diet rich in polyphenols enhances fat burning."
Resveratrol Promoted Fat Browning in In Vitro Studies
When the researchers studied the effects of resveratrol on brown adipogenic differentiation of inguinal WAT (iWAT) stromal vascular cells (SVCs), they found that higher concentrations (20 to 40 micrometers) of the polyphenol significantly (P<0.01) inhibited lipid accumulation in the differentiated iWAT SVCs. It also suppressed the expression of adipogenic markers PPAR-gamma and aP2. At concentrations of ≤10 micrometers, which is closer to plasma concentrations, resveratrol had no effect on lipid accumulation.
Resveratrol was found to significantly increase mRNA and/or protein expression of brown adipocyte markers, including uncoupling protein 1 (UCP1), PR domain-containing 16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty acids protein 3, peroxisome proliferator-activated receptor-gamma coactivators 1-alpha, cytochrome c, and pyruvate dehydrogenase in differentiated iWAT SVCs.
These findings suggest that resveratrol induces brown-like adipocyte formation in vitro, the researchers wrote.
Simultaneously, resveratrol enhanced AMP-activated protein kinase alpha 1 phosphorylation and differentiated SVC oxygen consumption.
AMPK alpha 1 Critical Mediator of Action
"Such changes were absent in cells lacking AMPK alpha 1, showing that AMPK alpha 1 is a critical mediator of resveratrol action," the researchers wrote.
When the researchers fed 5-month-old CD1 female mice a high-fat diet with or without 0.1% of resveratrol, they found that resveratrol feeding resulted in significant decreases in body weight gain compared with the control diet when challenged with a high-fat diet.
"Our findings confirmed the body fat-lowering effects of resveratrol, which have been reported in both animals and humans," the researchers wrote. "We found that resveratrol resulted in decreased adipocyte size in WAT, which is in agreement with a recent report in humans. More importantly, we observed brown-like adipocytes, with an appearance of multiocular lipid droplets, in iWAT, which has not been observed before."
Taken as a whole, the findings suggest that polyphenols like resveratrol enhance the oxidation and thermogenesis of white fat.
"Our results demonstrated that resveratrol induces the browning of mouse iWAT by promoting the expression of brown adipocyte selective genes through the activation of AMPK alpha 1," the researchers wrote.
The research was funded by the National Institutes of Health, the Natural Science Foundation of China, the Muscular Dystrophy Association, and the National Science Foundation.
The researchers declared no relevant relationships with industry.
- Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
- Primary Source
International Journal of Obesity
Source Reference: Wang S, et al "Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase" Inter J Obesity 2015; 39: 967-976.
one. It seems as though there is a common denominator here as we all have suspected.
