Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity.
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 8h 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.
Department of Medicine, Division of Endocrinology and Metabolism, UC San Diego, La Jolla, CA 92093, USA.
Heekyung
H
Chung
Department of Medicine, Division of Endocrinology and Metabolism, UC San Diego, La Jolla, CA 92093, USA.
Winjet
W
Chou
Department of Medicine, Division of Endocrinology and Metabolism, UC San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, UC San Diego, La Jolla, CA 92093, USA; Department of Family Medicine and Public Health, UC San Diego, La Jolla, CA 92093, USA.
Dorothy D
DD
Sears
Moores Cancer Center, UC San Diego, La Jolla, CA 92093, USA; Department of Family Medicine and Public Health, UC San Diego, La Jolla, CA 92093, USA.
Ruth E
RE
Patterson
Department of Medicine, Division of Endocrinology and Metabolism, UC San Diego, La Jolla, CA 92093, USA; Moores Cancer Center, UC San Diego, La Jolla, CA 92093, USA; VA San Diego Healthcare System, San Diego, CA 92161, USA.
Nicholas J G
NJ
Webster
Moores Cancer Center, UC San Diego, La Jolla, CA 92093, USA; Department of Pathology, UC San Diego, La Jolla, CA 92093, USA. Electronic address: lellies@ucsd.edu.
Lesley G
LG
Ellies
D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D002149:Energy Intake; D005234:Fatty Liver / Q000178:diet therapy*; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005943:Gluconeogenesis / Q000235:genetics; D007333:Insulin Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology*; D017698:Postmenopause
Hepatosteatosis; Insulin resistance; Obesity; Postmenopausal; Time-restricted feeding