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2013 ; 62
(4
): 1121-30
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Angiotensin 1-7 as means to prevent the metabolic syndrome: lessons from the
fructose-fed rat model
#MMPMID23250359
Marcus Y
; Shefer G
; Sasson K
; Kohen F
; Limor R
; Pappo O
; Nevo N
; Biton I
; Bach M
; Berkutzki T
; Fridkin M
; Benayahu D
; Shechter Y
; Stern N
Diabetes
2013[Apr]; 62
(4
): 1121-30
PMID23250359
show ga
We studied the effects of chronic angiotensin 1-7 (Ang 1-7) treatment in an
experimental model of the metabolic syndrome, i.e., rats given
high-fructose/low-magnesium diet (HFrD). Rats were fed on HFrD for 24 weeks with
and without Ang 1-7 (576 µg/kg/day, s.c., Alzet pumps). After 6 months, Ang
1-7-treated animals had lower body weight (-9.5%), total fat mass (detected by
magnetic resonance imaging), and serum triglycerides (-51%), improved glucose
tolerance, and better insulin sensitivity. Similar metabolic effects were also
evident, albeit in the absence of weight loss, in rats first exposed to HFrD for
5 months and then subjected to short-term (4 weeks) treatment with Ang 1-7. Six
months of Ang 1-7 treatment were associated with lower plasma renin activity
(-40%) and serum aldosterone (-48%), less hepatosteatatitis, and a reduction in
epididymal adipocyte volume. The marked attenuation of macrophage infiltration in
white adipose tissue (WAT) was associated with reduced levels of the pP65 protein
in the epididymal fat tissue, suggesting less activation of the nuclear factor-?B
(NF?B) pathway in Ang 1-7-treated rats. WAT from Ang 1-7-treated rats showed
reduced NADPH-stimulated superoxide production. In single muscle fibers
(myofibers) harvested and grown ex vivo for 10 days, myofibers from HFrD rats
gave rise to 20% less myogenic cells than the Ang 1-7-treated rats. Fully
developed adipocytes were present in most HFrD myofiber cultures but entirely
absent in cultures from Ang 1-7-treated rats. In summary, Ang 1-7 had an
ameliorating effect on insulin resistance, hypertriglyceridemia, fatty liver,
obesity, adipositis, and myogenic and adipogenic differentiation in muscle tissue
in the HFrD rats.