Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity

Heekyung Chung, Winjet Chou, Dorothy D. Sears, Ruth E. Patterson, Nicholas J.G. Webster, Lesley G. Ellies

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background Menopause is associated with significant hormonal changes that result in increased total body fat and abdominal fat, amplifying the risk for metabolic syndrome and diseases such as diabetes, cardiovascular disease and cancer in postmenopausal women. Intermittent fasting regimens hold significant health benefit promise for obese humans, however, regimens that include extreme daytime calorie restriction or daytime fasting are generally associated with hunger and irritability, hampering long-term compliance and adoption in the clinical setting. Time-restricted feeding (TRF), a regimen allowing eating only during a specific period in the normal circadian feeding cycle, without calorie restriction, may increase compliance and provide a more clinically viable method for reducing the detrimental metabolic consequences associated with obesity. Methods We tested TRF as an intervention in a mouse model of postmenopausal obesity. Metabolic parameters were measured using Clinical Laboratory Animal Monitoring System (CLAMS) and we carried out glucose tolerance tests. We also stained liver sections with oil red O to examine steatosis and measured gene expression related to gluconeogenesis. Results Preexisting metabolic disease was significantly attenuated during 7 weeks of TRF. Despite having access to the same high fat diet (HFD) as ad libitum fed (ALF) mice, TRF mice experienced rapid weight loss followed by a delayed improvement in insulin resistance and a reduced severity of hepatic steatosis by having access to the HFD for only 8 h during their normal nocturnal feeding period. The lower respiratory exchange ratio in the TRF group compared with the ALF group early in the dark phase suggested that fat was the predominant fuel source in the TRF group and correlated with gene expression analyses that suggested a switch from gluconeogenesis to ketogenesis. In addition, TRF mice were more physically active than ALF fed mice. Conclusions Our data support further analysis of TRF as a clinically viable form of intermittent fasting to improve metabolic health due to obesity.

Original languageEnglish (US)
Pages (from-to)1743-1754
Number of pages12
JournalMetabolism: Clinical and Experimental
Volume65
Issue number12
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Fingerprint

Insulin Resistance
Obesity
Liver
Fasting
Gluconeogenesis
Metabolic Diseases
High Fat Diet
Compliance
Gene Expression
Abdominal Fat
Preexisting Condition Coverage
Hunger
Laboratory Animals
Insurance Benefits
Glucose Tolerance Test
Menopause
Adipose Tissue
Weight Loss
Cardiovascular Diseases
Eating

Keywords

  • Hepatosteatosis
  • Insulin resistance
  • Obesity
  • Postmenopausal
  • Time-restricted feeding

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity. / Chung, Heekyung; Chou, Winjet; Sears, Dorothy D.; Patterson, Ruth E.; Webster, Nicholas J.G.; Ellies, Lesley G.

In: Metabolism: Clinical and Experimental, Vol. 65, No. 12, 01.12.2016, p. 1743-1754.

Research output: Contribution to journalArticle

Chung, Heekyung ; Chou, Winjet ; Sears, Dorothy D. ; Patterson, Ruth E. ; Webster, Nicholas J.G. ; Ellies, Lesley G. / Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity. In: Metabolism: Clinical and Experimental. 2016 ; Vol. 65, No. 12. pp. 1743-1754.
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AB - Background Menopause is associated with significant hormonal changes that result in increased total body fat and abdominal fat, amplifying the risk for metabolic syndrome and diseases such as diabetes, cardiovascular disease and cancer in postmenopausal women. Intermittent fasting regimens hold significant health benefit promise for obese humans, however, regimens that include extreme daytime calorie restriction or daytime fasting are generally associated with hunger and irritability, hampering long-term compliance and adoption in the clinical setting. Time-restricted feeding (TRF), a regimen allowing eating only during a specific period in the normal circadian feeding cycle, without calorie restriction, may increase compliance and provide a more clinically viable method for reducing the detrimental metabolic consequences associated with obesity. Methods We tested TRF as an intervention in a mouse model of postmenopausal obesity. Metabolic parameters were measured using Clinical Laboratory Animal Monitoring System (CLAMS) and we carried out glucose tolerance tests. We also stained liver sections with oil red O to examine steatosis and measured gene expression related to gluconeogenesis. Results Preexisting metabolic disease was significantly attenuated during 7 weeks of TRF. Despite having access to the same high fat diet (HFD) as ad libitum fed (ALF) mice, TRF mice experienced rapid weight loss followed by a delayed improvement in insulin resistance and a reduced severity of hepatic steatosis by having access to the HFD for only 8 h during their normal nocturnal feeding period. The lower respiratory exchange ratio in the TRF group compared with the ALF group early in the dark phase suggested that fat was the predominant fuel source in the TRF group and correlated with gene expression analyses that suggested a switch from gluconeogenesis to ketogenesis. In addition, TRF mice were more physically active than ALF fed mice. Conclusions Our data support further analysis of TRF as a clinically viable form of intermittent fasting to improve metabolic health due to obesity.

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