الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Obesity is a rapidly growing pandemic that continues to be a major severe health
problem due to its association with various adverse health consequences. Obesity is
recognized as an energetic imbalance caused mainly by the increased consumption of highcalorie
foods. According to the WHO, the prevalence of obesity has tripled worldwide
since 1975. Pharmacotherapy, in combination wit
h lifestyle modification, may play a vital role in reversing the disease burden.
One of the most promising approaches appears to be the employment of
nanotechnology in the treatment of obesity. SPIONs are inorganic nanomaterials that show
interesting properties such as superparamagnetism and low toxicity. SPIONs have been
explored because of their potentiality in biomedical applications. It was demonstrated that
SPIONs influence the gene expression of genes involved in lipid and glucose metabolism
and therefore may be used as therapeutics for the treatment of diabetes and obesity.
The present study aimed to explore the anti-obesogenic potential of SPIONs
compared to orlistat in the rat model of obesity. Also, this study aimed to evaluate the
effect of coating and dosing of SPION, two types of SPIONs was tested depending on the
molecular weight of the PEG coat (550 and 2000 Da) each type of SPIONs was used in
two doses (22 and 44 μmol Fe/kg). The last aim of the study was to explore the possible
molecular mechanisms of SPIONs including inflammation, lipogenesis, insulin resistance,
mitochondrial biogenesis, and WAT browning.
The study was conducted on 72 male albino rats 2-3 months old. Obesity was
induced in the animals by feeding them with an obesogenic diet for 3 months. Animals
were classified into two groups: the control group (8 control rats), and the obesity group
which was subdivided into 8 subgroups (8 rats each); untreated obese group, orlistattreated
group, SPIONs-PEG-550 treated groups (at the dose of 22 and 44 μmol Fe/kg),
SPIONs-PEG-2000 treated groups (at the dose of 22 and 44 μmol Fe/kg) and combinationtreated
groups (orlistat plus SPIONs-PEG-550 or SPIONs-PEG-2000 at dose of 22 μmol
Fe/kg). After 8 weeks of treatment, rats were sacrificed then blood samples, WAT and
BAT were collected. Serum samples were used for the following assessments: FBG,
insulin level, lipid profile, kidney and liver function tests, NEFA, leptin level, and lipase
activity. WAT and BAT were used for the assessment of TNF-α, PGC-1α, UCP-1, SIRT-1,
and mtDNA-CN.
The HFD-obese rats developed the classical picture of obesity including heavier
weight, increased weight gains, hyperglycemia, IR, dyslipidemia, and elevated serum
leptin and NEFA levels, AST and ALT activities, urea and creatinine levels. Also, the
obese rats showed significant suppression in the expression of PGC-1α, SIRT-1, and UCP-
1 and a significant decline in mitochondrial DNA copy number in the WAT and BAT.
The present study for the first time reported a promising effect of SPIONs as an
anti-obesity agent that is superior to the conventionally used drug orlistat. SPIONs
treatments significantly ameliorate weight gain, hyperglycemia, insulin resistance,
dyslipidemia, leptin and NEFA levels in obese rats. At the molecular level, surprisingly
SPIONs treatments markedly corrected the disturbed expression of inflammatory genes
Summary & Conclusions
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and genes controlling mitochondrial biogenesis and functions in BAT and WAT. The
observed effects indicated SPIONs as a powerful inducer of WAT browning and activator
of BAT functions.
from the present study, we can conclude that:
1- HFD-model of obesity in male rats was associated with significant disturbances in
glucose/lipid metabolism, IR, elevated NEFA level, and leptin resistance.
2- Obese rats suffered from impaired BAT functions and mitochondrial biogenesis and
functions due to suppressed expression of PGC-1α, SIRT-1, and UCP-1 in both
WAT and BAT function.
3- SPIONs have anti-obesity properties through the amelioration of glucose and lipid
homeostasis, insulin sensitivity, leptin production, and gene expression.
4- The effects of SPIONs may be mediated through suppression of WAT expansion,
induction of WAT browning, and activation of BAT function.
5- The mechanism of action of SPIONs is mediated through inducing the expression
of thermogenic genes such as PGC-1α, SIRT-1, and UCP-1, and mitochondria
biogenesis in BAT and WAT.
6- SPIONs coated with PEG-2000 are more efficient anti-obesity agents than those
coated with PEG-550.
7- The combination of the low dose of SPIONs-PEG-2000 (22 μmol Fe/kg/week) with
daily orlistat has the best efficiency for the treatment of obesity.