The G protein α-subunit G_sα mediates receptor-stimulated cAMP production and is imprinted with reduced expression from the paternal allele in specific tissues. Disruption of the G_sα maternal (but not paternal) allele leads to severe obesity, hypertriglyceridemia, and insulin resistance in mice and obesity in patients with Albright hereditary osteodystrophy. Paternal deletion of a G_sα imprint control region (1A) leads to loss of tissue-specific G_sα imprinting. To determine whether the metabolic abnormalities resulting from disruption of the G_sα maternal allele could be reversed by loss of paternal G_sα imprinting, females with a heterozygous G_sα exon 1 deletion were mated to males with heterozygous deletion of the imprint control region (1A) to generate mice with maternal G_sα deletion (E1^m−), paternal 1A deletion (1A^p−), double mutants (E1^m−:1A^p−), and wild type. E1^m− mice developed obesity, glucose intolerance, insulin resistance, and hypertriglyceridemia, which were all normalized by the paternal 1A deletion in E1^m−:1A^p− mice. Obesity in E1^m− was associated with reduced energy expenditure and sympathetic nerve activity, and these were also normalized in E1^m−:1A^p− mice. 1A^p− mice had reduced body weight associated with proportional decreases in fat and lean mass as well as increased activity levels. The metabolic phenotype resulting from maternal G_sα deletion is rescued by a genetic lesion that leads to loss of tissue-specific G_sα imprinting, consistent with this phenotype being a direct consequence of G_sα imprinting in one or more specific tissues.