Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota

Guolin Li, Cen Xie, Siyu Lu, Robert G. Nichols, Yuan Tian, Licen Li, Daxeshkumar Patel, Yinyan Ma, Chad N. Brocker, Tingting Yan, Kristopher W. Krausz, Rong Xiang, Oksana Gavrilova, Andrew David Patterson, Frank J. Gonzalez

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases. White adipose beiging is a promising therapy for obesity and related metabolic diseases. Here, Li, Xie and colleagues find that an EODF regimen can selectively induce the beiging of white adipose tissue and subsequently ameliorate metabolic disorders in mice. Gut microbiota orchestrate the effects of EODF on beiging and metabolic improvement.

Original languageEnglish (US)
Pages (from-to)672-685.e4
JournalCell Metabolism
Volume26
Issue number4
DOIs
StatePublished - Oct 3 2017

Fingerprint

Fasting
Obesity
Microbiota
White Adipose Tissue
Metabolic Diseases
Thermogenesis
Gastrointestinal Microbiome
Fermentation
Insulin Resistance
Adipose Tissue
Lactic Acid
Acetates
Homeostasis
Up-Regulation
Transplantation
Pharmacology
Weights and Measures
Liver

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Li, Guolin ; Xie, Cen ; Lu, Siyu ; Nichols, Robert G. ; Tian, Yuan ; Li, Licen ; Patel, Daxeshkumar ; Ma, Yinyan ; Brocker, Chad N. ; Yan, Tingting ; Krausz, Kristopher W. ; Xiang, Rong ; Gavrilova, Oksana ; Patterson, Andrew David ; Gonzalez, Frank J. / Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota. In: Cell Metabolism. 2017 ; Vol. 26, No. 4. pp. 672-685.e4.
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abstract = "While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases. White adipose beiging is a promising therapy for obesity and related metabolic diseases. Here, Li, Xie and colleagues find that an EODF regimen can selectively induce the beiging of white adipose tissue and subsequently ameliorate metabolic disorders in mice. Gut microbiota orchestrate the effects of EODF on beiging and metabolic improvement.",
author = "Guolin Li and Cen Xie and Siyu Lu and Nichols, {Robert G.} and Yuan Tian and Licen Li and Daxeshkumar Patel and Yinyan Ma and Brocker, {Chad N.} and Tingting Yan and Krausz, {Kristopher W.} and Rong Xiang and Oksana Gavrilova and Patterson, {Andrew David} and Gonzalez, {Frank J.}",
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Li, G, Xie, C, Lu, S, Nichols, RG, Tian, Y, Li, L, Patel, D, Ma, Y, Brocker, CN, Yan, T, Krausz, KW, Xiang, R, Gavrilova, O, Patterson, AD & Gonzalez, FJ 2017, 'Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota', Cell Metabolism, vol. 26, no. 4, pp. 672-685.e4. https://doi.org/10.1016/j.cmet.2017.08.019

Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota. / Li, Guolin; Xie, Cen; Lu, Siyu; Nichols, Robert G.; Tian, Yuan; Li, Licen; Patel, Daxeshkumar; Ma, Yinyan; Brocker, Chad N.; Yan, Tingting; Krausz, Kristopher W.; Xiang, Rong; Gavrilova, Oksana; Patterson, Andrew David; Gonzalez, Frank J.

In: Cell Metabolism, Vol. 26, No. 4, 03.10.2017, p. 672-685.e4.

Research output: Contribution to journalArticle

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T1 - Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota

AU - Li, Guolin

AU - Xie, Cen

AU - Lu, Siyu

AU - Nichols, Robert G.

AU - Tian, Yuan

AU - Li, Licen

AU - Patel, Daxeshkumar

AU - Ma, Yinyan

AU - Brocker, Chad N.

AU - Yan, Tingting

AU - Krausz, Kristopher W.

AU - Xiang, Rong

AU - Gavrilova, Oksana

AU - Patterson, Andrew David

AU - Gonzalez, Frank J.

PY - 2017/10/3

Y1 - 2017/10/3

N2 - While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases. White adipose beiging is a promising therapy for obesity and related metabolic diseases. Here, Li, Xie and colleagues find that an EODF regimen can selectively induce the beiging of white adipose tissue and subsequently ameliorate metabolic disorders in mice. Gut microbiota orchestrate the effects of EODF on beiging and metabolic improvement.

AB - While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases. White adipose beiging is a promising therapy for obesity and related metabolic diseases. Here, Li, Xie and colleagues find that an EODF regimen can selectively induce the beiging of white adipose tissue and subsequently ameliorate metabolic disorders in mice. Gut microbiota orchestrate the effects of EODF on beiging and metabolic improvement.

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