Coffee pulp and silverskin modulate hippocampal and hypothalamic proteomes in rats with fructose-induced metabolic syndrome.

Abstract

Coffee pulp (CP) and silverskin (SSK), two major coffee industry by-products, were recently shown to ameliorate metabolic syndrome (MetS) features induced by high-fructose feeding in rats. This work investigated, using proteomic analysis, whether CP and SSK induce changes in the hypothalamus and hippocampus relevant to fructose-induced MetS. In the hippocampus, high fructose consumption altered pathways related to the extracellular matrix (ECM), ECM-receptor interaction, cell-cell adhesion, synaptic transmission, and neuronal excitability. A highly coherent functional module centered on basement membrane (BM) proteins (COL4A1, COL4A2, LAMA2, LAMA4 and LAMA5) was identified. CP and SSK produced proteomic signatures suggestive of structural remodeling, particularly involving BM-related proteins associated with age-dependent changes in BM stability, neurovascular function, and cognitive trajectories. Of note, changes in the abundance of three proteins associated with neurodegenerative diseases observed following fructose feeding were not observed in animals co-treated with CP (VCCG3) or SSK (RETSAT and S100A6). In the hypothalamus, fructose consumption altered proteins involved in neuronal signaling and calcium dynamics, metabolism and stress response, gene regulation, cytoskeletal organization, and membrane-associated processes. CP mainly affected pathways associated with the neuronal cell body, whereas SSK predominantly influenced GTP binding and membrane-bounded organelles. Overall, fructose induced specific proteomic alterations in the hippocampus and hypothalamus and, in the hippocampus, CP and SSK altered proteins associated with neurovascular function and cognitive trajectories, consistent with a potential association with neuroprotective processes in the context of fructose-induced MetS. Distinct proteomic signatures observed with CP and SSK under standard and high-fructose diets further indicate specific protective mechanisms of these coffee by-products.