👤 Peter U Amadi

Metabolic-dysfunction associated steatohepatitis (MASH) arises from sustained triglyceride overload of the intestine-liver axis, yet current therapies rarely coordinate intestinal lipid entry with hepatic triglyceride disposal. Here we identify a phenolic-acid fraction as a dual-compartment metabolic modulator that couples intestinal lipase inhibition to CPT1α-PPARα-dependent hepatic β-oxidation across species. Across species, we investigated the kinetics and metabolic actions of a phenolic fraction (PhAM) using recombinant lipase systems, epithelial transport assays, hepatocyte models, pharmacokinetics, diet-induced metabolic disease paradigms, quantitative histopathology, and a 24-week randomized placebo-controlled clinical trial. PhAM selectively suppresses pancreatic and intestinal lipases non-competitively, lowering V_max with minimal K_m change, resembling some features of orlistat, but via a distinct, non-covalent mechanism. In Caco-2 monolayers and ex vivo loops, it reduces apical-to-basolateral fatty-acid flux, depletes intracellular triglycerides, and limits luminal-to-plasma lipid transfer. PhAM is orally bioavailable, with measurable plasma exposure and prolonged intestinal residence. Under high-fat feeding, it increases fecal fat loss, attenuates post-lipid-load triglyceride excursions, and lowers hepatic triglycerides without altering ApoB secretion. Its triglyceride-lowering effect requires CPT1α-dependent mitochondrial import and PPARα activation, elevates β-hydroxybutyrate, and induces oxidative genes while sparing lipogenesis. In chronic MASH, PhAM reduces steatosis, ballooning, inflammation, and metabolic-dysfunction associated steatotic liver disease (MASLD) Activity Score. A 24-week clinical subgroup, defined by ultrasound and transaminase enrichment, showed dose-responsive improvements in ultrasonographic steatosis and metabolic biomarkers. Collectively, these findings define PhAM as a phenolic-acid-based agent that aligns intestinal lipid restriction with hepatic oxidative unloading, offering a mechanistically coherent framework for potentially addressing steatotic liver disease-associated metabolic features. Show less

Due to the widespread unorthodox use of nuts to improve cardiovascular health, this clinical trial was carried out to evaluate the efficacy of walnut as an adjuvant statin in hypertensive subjects. A single-blind placebo-controlled randomized clinical trial that lasted for 3 months. Forty-five screened hypertensive subjects on treatment, aged 45-65 years, were randomized into intervention and placebo groups according to their blood pressure defined by the American Heart Association criteria. Fifteen (15) normotensive subjects were also recruited for this study. The participants in the intervention group included daily 7 g of boiled walnut taken as snacks. The study was not controlled for type of diet and frequency of meals in a day. Low-density lipoprotein cholesterol (LDLc) was the primary endpoint for this study. The mean LDLc levels of the intervention groups (84.6 mg/dl and 79.7 mg/dl, respectively) were significantly (p < .005) lower than the placebo (137.6 mg/dl). The high-density lipoprotein cholesterol (HDLc) levels of the intervention groups were significantly higher than the placebo. The mean total cholesterol levels of the intervention groups were significantly lower than the placebo group. The intervention groups recorded a significantly lower systolic and diastolic blood pressure compared to the placebo. The supplementation of walnut significantly decreased the apolipoprotein E (APOE), proprotein convertase subtilisin kexin 9 (PCSK9), and cholesteryl ester transfer protein (CETP) activities relative to the placebo. The use of walnut as a statin adjuvant during hypertension treatment reduced LDLc levels within 42.1% and improved HDL levels by 33.6%, and the LDLc decrease related to reduced PCSK9 and APOE activities while the HDLc increase related to reduced CETP activities. Show less