Impairment of Peripheral Circadian Clocks Precedes Metabolic Abnormalities in ob/ob Mice

Daily mRNA expression profiles of clock and clock-controlled genes were substantially dampened in the liver and adipose tissue of 10-wk-old ob/ob mice compared to control mice.

• Ob/ob mice showed significantly reduced expression of circadian genes in peripheral tissues, unlike control mice.
• A low-calorie diet and leptin administration improved metabolic abnormalities in ob/ob mice to a similar extent.
• Leptin treatment specifically restored the impaired peripheral clocks in ob/ob mice.
• Reduced clock function was observed in the peripheral tissues of young ob/ob mice prior to any metabolic abnormalities.
• The impairment of peripheral clocks in ob/ob mice may be partially caused by leptin deficiency rather than metabolic issues.

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