. 2010 Nov 2;300(1):E3–E10. doi: 10.1152/ajpendo.00512.2010

Table 1.

Summary of mouse models in which genetic alterations or pharmacological interventions targeting skeletal muscle have been applied to understand how its modulation impacts metabolic dysfunction

		Phenotype¹		Tissue and Serum Parameters¹
	Diabetes Model	Global	Metabolic	Skeletal Muscle	Liver	Adipose Tissue	Serum	Key Refs.
Genetic alterations promoting a resistance-trained phenotype
Akt1 Tg Skeletal muscle, conditional	HF/HSD	↓ body weight	↓ glucose	↑ IIb fiber CSA	↓ lipids	↓CSA adipocytes	↓ leptin	35
		↑ muscle mass	↓ insulin	↓ FAO G/P	↑ FAO G/P		= FA
		↓ fat mass	↑ GT	↑ GTU G/P			= TG
			↑ IS				= TG
Myostatin KO or mutation	HFD	= /↓ body weight	↓ glucose	↑ type IIb fibers	↓ lipids	↓ inguinal, perigonadal and retroperitoneal depot weights	↓ leptin	26, 27, 51
	Aγ	= /↓ body weight	↓ insulin	↑ fiber CSA	↓ CD36		↓ resistin
	ob/ob	↑ muscle mass	↑ GT	↓ FAO G/P	↓ p-IRS-1 Ser³⁰⁷		↓ TNFα
		↓ fat mass	↑ IS					↓ Chol
ActRIIB DN Skeletal muscle	HFD	↓ body weight	↓ glucose	↑ fibers	↓ lipids	↓ CSA adipocytes	↓ leptin	26, 41
		↑ muscle mass	↓ insulin	↑ fiber CSA			↓ TG
		↓ fat mass	↑ GT
			↑ IS
Genetic alterations promoting an endurance-trained phenotype
PGC-1α Tg² Skeletal muscle	HFD	= body weight	= glucose	↑ type I fibers	= glucose production		= FA	17, 45
		= muscle mass	= insulin	↑ mitochondria			= TG
		= fat mass	↓ IS	↑ FAO G/P			= Chol
				↑ TG/DAG
PGC-1α Tg² Skeletal muscle	Aging	↓ body weight	↓ glucose	As above			↓ TNFα	87
		↑ muscle mass	↑ GT	↑ capillary dens.			↓ IL-6
		↓ fat mass	↑ IS	↑ p-Akt, -mTOR			↓ Tg
PPARδ Tg Skeletal muscle	HFD	↓ body weight	↓ glucose	↑ type I fibers		↓CSA adipocytes		85
		ob/ob	↓ fat mass	↓ insulin	↑ mitochondria		↓ inguinal and retroperitoneal depot weights
			↑ GT	↑ FAO G
			↑ IS	↓ TG
Calcineurin TG Skeletal muscle	HFD	= body weight	= glucose	↑ glucose uptake				56, 65, 91
		= muscle mass	= insulin	↑ FAO
		↓ fat mass	↑ GT	↑ FAO G/P
			↑ IS	↑ GTU G/P
Pharmacological interventions promoting a resistance-trained phenotype
Myostatin antibody 6 wk	ob/ob	= body weight	↓ glucose	↑ fiber CSA	= lipids	↑ FAO G/P	↑ Adipoq	9
		↑ muscle mass	↓ insulin	↓ TG	= FAO G	↑ GTU G/P	↑ FAO G
		= fat mass	↑ GT	↑ GTU G	= GTU G
sActRIIB 10 wk	HFD	= body weight	↓ glucose	↑ fiber CSA	↓ glucose production	= glucose uptake	↓ leptin	2
		↑ muscle mass	= insulin				↓ Chol
		↓ fat mass	↑ IS				↑ Adipoq
Pharmacological intervention promoting an endurance-trained phenotype
PPARδ agonist, 3–8 wk	HFD	↓ body weight	=/↓ glucose	↑ FAO	= FAO	↓ visceral and subcutaneous depot weights	↓ FFA	9, 77, 85
	ob/ob	= muscle mass	↓ insulin	↑ FAO G/P	↓ lipids		↓ TG
		↓ fat mass	↑ GT	↓ lipids			↑ HDL
			↑ IS

Compared with noninduced, wild-type or vehicle-treated control mice.

Both studies were conducted in transgenic mice expressing PGC-1α under control of the muscle creatine kinase promoter/enhancer as originally detailed in Ref. 44.

Tg, transgenic; ActRIIB, activin type IIB receptor; HF/HSD, high-fat high-sucrose diet; GT, glucose tolerance; IS, insulin sensitivity; CSA, cross-sectional area; FAO, fatty acid oxidation; G, genes; P, proteins; GTU, glucose transport and utilization; TG, triglycerides; FA, fatty acids; KO, knockout; HFD, high-fat diet; Aγ, agouti lethal yellow mice; ob/ob, obese leptin-deficient mice; Chol, cholesterol; DN, dominant negative; DAG, diacylglycerol; dens., capillary density capillary; Adipoq, adiponectin; HDL, high-density lipoproteins.