Research

Muscle Loss in Obese Mice

Mice were fed a high-fat diet until they became obese followed by determination of total muscle proteins and muscle weight. Data in the Table indicates that ZKPr1 statistically significantly reversed the obesity related loss of muscle proteins, regardless of whether it was delivered orally (daily for 3 weeks), subcutaneously (S.C.; once weekly; 10 weeks) or intravenously (I.V.; once weekly; 8 weeks) with 7 mice in each set.

TABLE [pZKPR1 and rZKPR1 are highly (96-98%) purified or recombinant, respectively].
SD is standard diet; HFD is high fat diet; I.V. and S.C. are intravenous and subcutaneous, respectively.

The mechanism of ZKPr1 effect may involve several mechanisms (some of them are included in the Figure below), each being investigated based on leads already provided by ongoing experiments:

1. ZKPr1 is an anti-apoptosis protein helping survival of muscle cells under stress caused by, for example, obesity related factors and aging related altered metabolism.

2. ZKPr1 inactivates lipopolysaccharide (LPS), an important inducer of inflammation in obesity. In obese people the intestine becomes leaky and allows transport of LPS into the bloodstream that leads to muscle breakdown shown in the Figure.

3. In vitro, ZKPr1 inhibits myostatin, a negative regulator of muscle cell viability. Such an effect of ZKPr1 may well occur in vivo as well.

Muscle Loss in Old Mice

Once a week treatment of 18 months old mice with low, commercially affordable, dose of ZKPr1 reduced muscle protein loss by about 80% resulting in increased life span. A connection between the effects of ZKPr1 on skeletal muscle proteins and increased survival is very likely, and the underlying mechanism is presently under study. Regardless of the mechanism, these findings are likely to apply to aging humans as well and merit further studies in that direction.