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Circulating factors potentiate muscle atrophy in human heart failure by impairing the anabolic response to feeding
Author(s) -
Toth Michael J.,
Ward Kimberly,
Velden Jos,
Miller Mark S.,
Matthews Dwight E.,
VanBuren Peter,
LeWinter Martin M.,
Ades Philip A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1064.2
Subject(s) - anabolism , medicine , endocrinology , heart failure , myogenesis , protein catabolism , hyperinsulinemia , myocyte , biology , insulin , insulin resistance , amino acid , biochemistry
Patients with chronic heart failure (HF) experience muscle atrophy during the course of the disease, although the mechanisms are not well‐defined. We measured leg phenylalanine balance and kinetics in HF patients and controls under fasting and euglycemic‐hyperinsulinemic‐hyperaminoacidemic conditions and examined whether the protein metabolic response was correlated to circulating inflammatory markers. HF had no effect on fasting protein balance or kinetics, but the anabolic response to hyperinsulinemia‐hyperaminoacidemia was reduced by more than 50% in patients due to impaired suppression of protein breakdown. The diminished anabolic response was related to greater circulating interleukin‐6 levels (P<0.05). To clarify a role for circulating factors in the diminished anabolic response, cultured C2C12 myotubes were subjected to a starvation protocol and then refed (18 h) in media supplemented with the plasma (2%) from HF patients or controls. After the refeeding period, the protein content of myotubes was slightly (8%), but not significantly, lower in HF patients versus controls. Notably, reduced protein content was related (P<0.05) to higher circulating C‐reactive protein levels. Collectively, our results suggest that heart failure impairs the muscle protein anabolic response to meal‐related stimuli and implicate circulating inflammatory mediators in this impairment.