Table 2.

Key clock genes associated with metabolic phenotypes in transgenic mice

Gene	Findings
Circadian locomotor output cycles kaput (Clock)	Clock-mutant mice developed obesity, hyperlipidemia, hyperinsulinemia, hyperphagia (214, 215) and hyperglycemia (216).
Nuclear receptor subfamily 1 group D member 1/2 (NR1D1/2 Rev-erb α/β)	Whole-body KO mice had increased adiposity and hyperglycemia compared with WT mice (217). SCN-specific KO of Rev-erb α and β results in increased weight gain, higher fasting blood glucose, and increased cumulative food intake under 24-h darkness (218).
Period 1/2 (Per1/2)	Per2-mutant (nonfunctional) mice show altered feeding patterns and reduced fasting blood glucose (219) and lack of a food-anticipatory response (220); Per1/2-KO mice show abnormal feeding behavior, consuming 50% of their total intake in the light cycle (221).
Cryptochrome 1/2 (Cry 1/2)	Cry1/2-KO mice rapidly gain weight on HFD (222), whereas Cry1-KO mice are protected from weight gain on HFD (223).
Brain and muscle ARNT-like 1 (Bmal1)	Brain-clock Bmal1 KO led to an increase in eating during the inactive phase (224); pancreatic Bmal1 KO resulted in impaired insulin secretion and hyperglycemia (216); SCN-specific Bmal1-KO mice gained weight under conditions of constant darkness (225); myeloid-specific Bmal1-KO mice displayed attenuated HFD-induced atherosclerosis (226).

HFD, high-fat diet; KO, knockout; SCN, suprachiasmatic nucleus; WT, wild type.