Investigating the effect of khat (catha edulis) on selected obesity markers and pathways in C57BL/6J male mice / Mustafa Ahmed Al-Shagga
In East African and South Western Arabian populations, Catha edulis (khat) is believed to suppress appetite and reduce body weight. First, this study conducted a systematic review of the literature on the effects of khat and its active alkaloid cathinone on body weight and appetite regulation....
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Format: | Thesis |
Published: |
2021
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Online Access: | http://studentsrepo.um.edu.my/13270/4/mustafa.pdf http://studentsrepo.um.edu.my/13270/ |
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Institution: | Universiti Malaya |
Summary: | In East African and South Western Arabian populations, Catha edulis (khat) is
believed to suppress appetite and reduce body weight. First, this study conducted a
systematic review of the literature on the effects of khat and its active alkaloid cathinone
on body weight and appetite regulation. Second, this study investigated the effect of khat
and cathinone on selected metabolic and histopathologic parameters and their influence
on the expression of obesity-related genes in high-fat diet-induced obese mice. Forty-two
male C57BL/6J mice were divided into seven groups (n= 6); normal diet control treated
with vehicle (NDC), normal diet treated with 200 mg/kg khat extract (NDK200), high fat
diet control treated with vehicle (HFDC), high-fat diet treated with 200 mg/kg khat extract
(HFDK200), high-fat diet treated with 400 mg/kg khat extract (HFDK400), high-fat diet
treated with 3.2 mg/kg cathinone (HFDCAT) and high-fat diet treated with 15 mg/kg
orlistat (HFDO). The assigned diet was followed for 16 weeks, with treatment starting
from week 9 onwards. Treatments were carried out once daily by gastric gavage for 8
weeks.
The systematic review synthesised 15 studies and found that khat consumption is
associated with weight loss, appetite suppression, and relatively low triglyceride levels.
Nevertheless, studies on the effect of khat on leptin and insulin levels have yielded mixed
results, with no mechanistic studies available on the anti-obesity effect of this plant. In
our animal experiment. HFD groups gained significant body weight at week 8 than ND
groups (p<0.05). After 8 weeks of khat administration, the weight gains of HFDK400
(3.1 ± 0.6 g), HFDCAT (-0.4 ± 2.2 g), and HFDO (3.5 ± 3.8 g) groups gained less weight
than the HFDC (9.6 ± 4.3 g) group. The NDK200-treated mice ate less than the NDC
group, but the differences in weight gain were not statistically significant. HFDK200,
HFDK400, and HFDCAT had less fatty liver and lee fat body mass (p<0.05) and serum
triglycerides (p<0.05) than the HFDC group. A dose-dependent decrease in serum leptin
was observed in response to khat administration, and it was statistically significant in
HFDK400 treated mice (p<0.01), whereas the HFDCAT group was associated with low
insulin (p<0.01), low leptin (p<0.001) and low peptide YY (PYY) (p<0.05) levels than
the HFDC group. The adiponectin levels in HFDO (3.13 ± 0.3 ng/ml), HFDK200 (3.14 ±
0.6 ng/ml) and HFDK400 (3.16 ± 0.2 ng/ml) treated groups were significantly (p<0.05)
higher than the HFDC (1.20 ± 0.1 ng/ml) group. On the contrary, HFDCAT serum
iv
interleukin-6 (IL-6) (62.7 ± 10.1 pg/ml), was significantly (p<0.05) lower than HFDC
(110.1 ± 16.3 pg/ml), whereas serum resistin in HFDK200 (6.0 ±2.0 ng/ml), HFDK400
(3.8 ± 1.7 ng/ml) and HFDCAT (3.3 ± 1.5 ng/ml) groups showed significantly lower
levels (p<0.05) compared to HFDC (12.6 ± 1.4 ng/ml). Bone structural
histomorphometric parameters showed significantly higher bone volume density
(BV/TV) and less trabecular separation in HFDK200 and HFDCAT than the HFDC group
(p<0.05). However, HFDCAT had high osteoblast and osteoclast surfaces compared to
both khat extract treated groups.
The gene expression findings of adipose tissue showed upregulation of the lipolysis
pathway gene: adipose triglyceride lipase (PNPLA-2), which reported 3.3, 13.3, 19.3, and
17.7-fold changes for HFDO, HFDK200, HFDK400 (p<0.05), and HFDCAT,
respectively, compared to the HFDC vehicle-treated mice. Hormone-sensitive lipase
(LIPE) gene expression showed 4.4, 11.2, 19.9, and 11.1-fold changes upregulation for
HFDO, HFDK200, HFDK400 (p<0.05), and HFDCAT, respectively compared to the
HFDC group. HFDK400-treated mice were also associated with significant
overexpression of insulin receptor (INSR) (3.9-fold change), mechanistic target of
rapamycin (mTOR) (6.6-fold change), and Glut4 (3.9-fold change), whereas insulin
substrate-1 was upregulated in HFDCAT and HFDK200 (p<0.05) compared to the HFDC
group. Adiponectin (ADIPQ) showed 51- and 67-fold changes (p<0.05) for both
HFDK200 and HFDK400, respectively. Hypothalamic gene expressions revealed a
significant (p<0.05) upregulation of agouti-related peptide (AGRP) and cocaine�amphetamine regulated peptide (CARTP) genes in HFDK400 (2.5 and 1.9, respectively)
and HFDCAT group (4.5 and 4.3, respectively). HFDK200-treated mice showed a
significant (p<0.05) overexpression of hypothalamic IL-6 (3-fold change), while the
orlistat-treated group did not show any significant hypothalamic gene changes than the
HFDC group. In conclusion, the animal study demonstrated a significant effect of khat
400 mg/kg and cathinone on reducing body weight gain in diet-induced obese mice, and
this reduction is superior to orlistat. This study supports systematic review findings and
provides novel possible peripheral and central anti-obesity mechanisms of khat and
cathinone.
Keywords: Khat; Catha edulis; Cathinone; Obese mice; Mechanism of action
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