Chickpea Protein Hydrolysate Ameliorates the Impact of Feeding a High-Fat-Diet-Induced Obesity in Mice by Modulating Inflammation

OBJECTIVES: To evaluate the efficacy of a chickpea (Cicer arietinum) protein hydrolysate (CPH) on ameliorating markers of obesity in a mouse model of metabolic dysfunction when fed a high fat diet. METHODS: CPH was produced using an Alcalase® and Flavourzyme® dual-system. Fifty-two male C57BL/6J mice (6 weeks of age) were randomized into four groups (n = 13/group) and fed daily, for a period of 16 weeks, as follows: standard diet (SD), high-fat diet (HFD), HFD + 400 mg CPH/kg body weight (BW) (400 CPH), and HFD + 800 mg CPH/kg BW (800 CPH). BW was measured weekly and blood glucose biweekly via tail bleeding. Feces were collected during week 16. Tissue samples were collected at the end of the study. Protein expression was measured in blood plasma, and metabolites relative concentrations in feces. Gene expression analyses were performed on liver, adipose, and pancreas tissues. RESULTS: Weight gain for the 800 CPH group was significantly lower (19%, P < 0.01) than the weight gain in the HFD group. Both, adipose and liver tissue weights were significantly lower (12% and 26%, P < 0.05, respectively) in 800 CPH than in HFD. Group 800 CPH had significantly reduced (P < 0.05) plasma protein levels of interleukin (IL)-1 α (14%), IL-4 (35%), IL-9 (32%), lymphotactin (37%), MCP-1 (48%), MIP-1 γ (40%), and TNF- α (40%) as compared to the HFD group. In liver, the 400 CPH group had upregulation (fold change [FC] >2) of genes related to lipid metabolism (Acsl4) and adipokine signaling (Adipor2) and downregulation (FC 0.3–0.5) of genes related to insulin signaling (Pik3r1, Ikbkb, Map2k1) when compared to HFD. In adipose tissue, the 800 CPH group modulated (FC > 2) genes related to inflammation (IL1B and IL18R1), and carbohydrate metabolism (Hk2) compared to the HFD group. The 400 CPH group had significant (FC > 2) upregulation of Tlr4 in pancreas tissue as compared to HFD. More than two hundred metabolites were identified in feces; branched-chain amino acids leucine and isoleucine decreased their relative concentrations in 800 CPH in comparison to HFD. CONCLUSIONS: Findings indicated that mice fed CPH had lower BW, reduced levels of inflammatory proteins in plasma, downregulated genes related to insulin signaling, and upregulated genes related to lipid metabolism, and adipokine signaling. FUNDING SOURCES: USDA Pulses Division.