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Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity.
Metabolism. 2016 Dec; 65(12):1743-1754.M

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 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.

Authors+Show Affiliations

Department of Medicine, Division of Endocrinology and Metabolism, UC San Diego, La Jolla, CA 92093, USA.Department of Medicine, Division of Endocrinology and Metabolism, UC San Diego, La Jolla, CA 92093, USA.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.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.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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27832862

Citation

Chung, Heekyung, et al. "Time-restricted Feeding Improves Insulin Resistance and Hepatic Steatosis in a Mouse Model of Postmenopausal Obesity." Metabolism: Clinical and Experimental, vol. 65, no. 12, 2016, pp. 1743-1754.
Chung H, Chou W, Sears DD, et al. Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity. Metabolism. 2016;65(12):1743-1754.
Chung, H., Chou, W., Sears, D. D., Patterson, R. E., Webster, N. J., & Ellies, L. G. (2016). Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity. Metabolism: Clinical and Experimental, 65(12), 1743-1754. https://doi.org/10.1016/j.metabol.2016.09.006
Chung H, et al. Time-restricted Feeding Improves Insulin Resistance and Hepatic Steatosis in a Mouse Model of Postmenopausal Obesity. Metabolism. 2016;65(12):1743-1754. PubMed PMID: 27832862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity. AU - Chung,Heekyung, AU - Chou,Winjet, AU - Sears,Dorothy D, AU - Patterson,Ruth E, AU - Webster,Nicholas J G, AU - Ellies,Lesley G, Y1 - 2016/09/22/ PY - 2016/04/11/received PY - 2016/09/07/revised PY - 2016/09/12/accepted PY - 2016/11/12/entrez PY - 2016/11/12/pubmed PY - 2017/5/17/medline KW - Hepatosteatosis KW - Insulin resistance KW - Obesity KW - Postmenopausal KW - Time-restricted feeding SP - 1743 EP - 1754 JF - Metabolism: clinical and experimental JO - Metabolism VL - 65 IS - 12 N2 - 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. SN - 1532-8600 UR - https://www.unboundmedicine.com/medline/citation/27832862/Time_restricted_feeding_improves_insulin_resistance_and_hepatic_steatosis_in_a_mouse_model_of_postmenopausal_obesity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0026-0495(16)30112-3 DB - PRIME DP - Unbound Medicine ER -