BACKGROUND: Obese adults are prone to develop metabolic and @entity65 . Furthermore, over-weight expectant mothers give birth to large babies who also have increased likelihood of developing metabolic and @entity65 . Fundamental advancements to better understand the pathophysiology of @entity28 are critical in the development of anti- @entity28 therapies not only for this but also future generations. Skeletal muscle plays a major role in fat metabolism and much work has focused in promoting this activity in order to control the development of @entity28 . Research has evaluated myostatin inhibition as a strategy to prevent the development of @entity28 and concluded in some cases that it offers a protective mechanism against a high-fat diet. METHODS: Pregnant as well as virgin myostatin null @entity19 and age matched wild type animals were raised on a high fat diet for up to 10 weeks. The effect of the diet was tested on skeletal muscle, liver and fat. Quantitate PCR, Western blotting, immunohistochemistry, in-vivo and ex-vivo muscle characterisation, metabonomic and lipidomic measurements were from the four major cohorts. RESULTS: We hypothesised that myostatin inhibition should protect not only the mother but also its developing foetus from the detrimental effects of a high-fat diet. Unexpectedly, we found muscle development was attenuated in the foetus of myostatin null @entity19 raised on a high-fat diet. We therefore re-examined the effect of the high-fat diet on adults and found myostatin null @entity19 were more susceptible to diet-induced @entity28 through a mechanism involving impairment of inter-organ fat utilization. CONCLUSIONS: Loss of myostatin alters @entity844 uptake and oxidation in skeletal muscle and liver. We show that abnormally high metabolic activity of fat in myostatin null @entity19 is decreased by a high-fat diet resulting in excessive adipose deposition and lipotoxicity. Collectively, our genetic loss-of-function studies offer an explanation of the lean phenotype displayed by a host of animals lacking myostatin signalling.

Investigating mechanisms underpinning the detrimental impact of a high-fat diet in the developing and adult hypermuscular myostatin null XXXX .

@entity19 :: ('10090', 'Species') :: ['mice'] @entity844 :: ('CHEBI:35366', 'Chemical') :: ['fatty acid'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular diseases'] @entity28 :: ('MESH:D009765', 'Disease') :: ['obesity']
@entity19 :: (10090,Species) :: ['mouse']
