Table 1.

Differential phosphorylation ratio of twenty-seven proteins related to the insulin, AKT, mTOR, FoxO, AMPK, and MAPK pathways in HepG2 cells in response to the treatment with palmitic acid (PA, 500 µmol L⁻¹) and the co-treatment with PA and the phytochemical-rich aqueous extract from the cocoa shell (CAE, 100 µg mL⁻¹).

Target Protein	Phosphosite	Effect of Phosphorylation	Relative Phosphorylation		Fold Change
			PA	CAE	CAE/PA	p-Value
Insulin signaling
IGF1R	Y1165	Induces activity	0.23 ± 0.02	0.45 ± 0.04	1.99 ± 0.22	0.033 *
INSR	Y1189	Induces activity	0.68 ± 0.05	1.96 ± 0.11	2.87 ± 0.21	0.009 **
IRS-1	S318	Inhibits molecular association	0.06 ± 0.01	0.26 ± 0.03	4.28 ± 0.48	0.020 *
SHC-1	Y427	Induces activity	0.18 ± 0.02	0.32 ± 0.05	1.77 ± 0.35	0.117
SHIP-1	Y1020	Induces activity	0.13 ± 0.01	0.30 ± 0.05	2.21 ± 0.39	0.060
SHP-2	T542	Induces molecular association	0.34 ± 0.03	0.56 ± 0.04	1.65 ± 0.21	0.081
PI3K-AKT-PKB signaling
AKT	S473	Induces activity	0.57 ± 0.04	1.54 ± 0.09	2.71 ± 0.21	0.011 *
BAD	S112	Inhibits molecular association	0.29 ± 0.02	1.08 ± 0.11	3.65 ± 0.32	0.008 **
GSK3α	S21	Inhibits activity	0.46 ± 0.03	1.31 ± 0.08	2.85 ± 0.20	0.008 **
GSK3β	S9	Inhibits activity	0.67 ± 0.02	1.44 ± 0.12	2.15 ± 0.17	0.012 *
PDK1	S241	Induces activity	0.63 ± 0.02	1.24 ± 0.08	1.97 ± 0.14	0.013 *
PTEN	S370	Inhibits activity	0.40 ± 0.05	1.85 ± 0.08	4.65 ± 0.39	0.008 **
mTOR/S6K signaling
4E-BP1	T36	Inhibits activity	0.95 ± 0.03	1.77 ± 0.39	1.86 ± 0.35	0.075
EIF4E	S209	Inhibits molecular interaction	0.10 ± 0.01	0.22 ± 0.01	2.12 ± 0.24	0.038 *
mTOR	T2448	Induces activity	0.73 ± 0.07	1.64 ± 0.17	2.23 ± 0.29	0.038 *
p70S6K	T421/S424	Induces activity	0.61 ± 0.02	0.94 ± 0.09	1.54 ± 0.17	0.055
PRAS40	T246	Inhibits activity	0.63 ± 0.04	1.38 ± 0.16	2.19 ± 0.26	0.026 *
rpS6	S235/236	Induces activity	0.87 ± 0.08	2.21 ± 0.06	2.55 ± 0.19	0.014 *
FoxO signaling
FOXO3	S413	Induces activity	0.02 ± 0.00	0.04 ± 0.01	2.12 ± 0.39	0.074
p27	T198	Inhibits molecular interaction	0.38 ± 0.05	1.00 ± 0.10	2.61 ± 0.38	0.038 *
AMPK signaling
AMPKα	T172	Induces activity	0.65 ± 0.03	1.55 ± 0.09	2.38 ± 0.16	0.009 **
LKB1	S428	Induces activity	0.44 ± 0.05	1.00 ± 0.05	2.24 ± 0.25	0.036 *
p53	S15	Induces activity	0.60 ± 0.03	1.70 ± 0.13	2.85 ± 0.20	0.007 *
MAPK signaling
ERK1/2	T202/Y204 Y185/187	Induces activity	0.50 ± 0.02	1.51 ± 0.10	2.99 ± 0.19	0.006 **
Raf-1	S301	Inhibits activity	0.51 ± 0.06	1.48 ± 0.11	2.88 ± 0.33	0.022 *
RSK1	S380	Induces protein degradation	0.49 ± 0.03	1.19 ± 0.05	2.45 ± 0.15	0.008 **
RSK2	S386	Induces activity	0.71 ± 0.03	1.38 ± 0.05	1.96 ± 0.11	0.009 **

Results are reported as mean ± SD (n = 3). p-values followed by *, **, indicate a statistically significance difference between PA and CAE groups when subjected to the t-test (p < 0.05, p < 0.01, p < 0.001, respectively).