الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
According to the World Health Organization (WHO) by 2025, one in every five adults
globally will be obese. Lifestyle management is one of the weight-losing techniques that do
not require pills and/or surgery. Medical management of obesity is required for obese
individuals with a BMI > 30 kg/m2
or BMI ≥ 27 kg/m2 with obesity-related comorbidities.
Effective treatments are needed to reduce early deaths from obesity and reduce other obesity
risk factors. SPIONs’ physical, chemical, and magnetic properties, as well as their shape and
size, influence the wide spectrum of potential bio-applications which is used in biology,
medical diagnosis, and therapy.
Due to the importance of liver as a primary organ that organizes lipids homeostasis via a
complex network of biochemical, signaling, and cellular mechanisms. Lipid catabolism occurs in
mitochondria, and mitochondrial failure causes TG to build up in the liver. our studies were
designed to explore the possible impacts of SPIONs as anti-obesity agent in the liver of
experimental model of obesity, and to evaluate the hepatic effect of SPIONs during the treatment
of obesity, explore lipolytic pathway and mitochondrial biogenesis as the molecular targets of
SPIONs in the liver through their effect on gene expression of PGC-1α, SREBP1c, NRF1, NRF2,
and determination of mtDNA-CN via relative mtDNA expression.
This study was carried on 72 healthy male albino rats two months old with average weight
80-90 g. Rats were classified into two groups: group I: (Control group): contained 8 male rats
were fed with a normal chow during the experiment and were served as negative control. Group
II: (Obesity group): in which obesity was induced in 64 male rats over a three-month period by
continuing to feed them an obesogenic diet (per 100g diet) When the obese rats reached a
considerable weight; they were randomly subdivided into eight experimental subgroups (eight rats
each) as follows: GII-A: untreated obese male rats. GII-B: obese rats treated with an oral dose of
orlistat (30 mg/kg daily for two months). GII-C: obese rats treated with SPION-550 intravenously
in a dose of 22 μmol Fe/kg one time per week for two months. GII-D: obese rats with SPION-550
intravenously in a dose of 44 μmol Fe/kg once a week for two months. GII-E: obese rats treated
with combination of SPION- 550 intravenously at lower dose and orlistat in a dose of 30 mg/kg
daily for two months. GII-F: obese rats treated with SPION-2000 intravenously in a dose of 22
μmol Fe/kg one time per week for two months. GII-G: obese rats treated with SPION- 2000
intravenously in a dose of 44 μmol Fe/kg once a week for two months. GII-H: obese rats treated
with combination of SPION- 2000 intravenously at lower dose one time per week and orlistat in a
dose 30 mg/kg daily for two months.
At the end of the experimental period, all rats were sacrificed after overnight fasting, blood
samples and liver tissues were collected for assessment of the studied parameters.
Obese rats have the classical characteristics of obesity including elevated weight gains,
hyperglycemia, elevated insulin resistance, dyslipidemia, and elevated serum AST, and ALT, they
Also showed induced hepatic oxidative stress, impairment in glutathione system, significant
suppression in the expression of PGC-1α, NRF1, and NRF2 and marked decline in mitochondrial
DNA copy number.
These results support the promising anti-obesity effects of SPIONs especially when
combined with orlistat. Also, the study provides solid evidence for the anti-steatosis effects of
SPIONs in the rat model of obesity. The weekly intravenous doses of SPIONs (22, or 44 μmol
Fe/kg) coated with PEG of two molecular weights (PEG 550 Dalton and PEG 2000 Dalton)
effectively ameliorate the multiple hepatic abnormalities associated with the obese rat model
through their insulin sensitizing, lipotropic, antioxidant, anti-lipogenic, and mitochondrial boosting
effects.
Summary & Conclusions
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The effect of SPIONs was elicited through the amelioration of mitochondrial biogenesis by
upregulation of the relative expression of PGC-1α and NRF1. Moreover, SPIONs’ treatment also
led to inhibition of liver lipogenesis by downregulating the expression of SREBP1c, reduction of
MDA liver content, decreasing of both FBG and HOMA-IR, marked reduction of lipid profile,
improving both level of AST and ALT enzyme activities compared with untreated obese rats and
elevation of GSH liver content. SPIONs coated with PEG-2000 are more efficient anti-obesity than
those coated with PEG-550 and daily dose of orlistat combined with low dose of SPION-2000
showed the most efficient anti-obesity treatment. Accordingly, SPIONs could be used alone or in
combination with orlistat for treatment of obesity.
from the results of these study, it can be concluded that
1. Obese rat model was associated with many metabolic disturbances include
dyslipidemia, hyperglycemia, insulin resistance, accumulation of triglycerides in the
liver,and abnormalities in the redox status of the hepatic tissues
2. Obesity was associated with impaired hepatic mitochondrial biogenesis and marked
decline in mtDNA-CN
3. The promising anti-obesity and anti-steatotic potential of SPIONs in obese rats
4. The mechanism of action of SPIONs may be mediated through:
a- Insulin sensitizing action.
b- Suppressing the expression of lipogenesis gene; SREBP-1c.
c- Induction of hepatic antioxidant systems.
d- Inducing the hepatic expression of PGC-1α and NRF-1.
e- Boosting mitochondrial biogenesis and functionality.
5. Orlistat may be used as an adjuvant treatment