A lipid-rich gestational diet predisposes offspring to nonalcoholic fatty liver disease: a potential sequence of events

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. It affects 20%–30% of the US population, and it is increasing worldwide. Recently, the role of lipid-rich maternal gestational nutrition in spurring the development of NAFLD among offspring has been indicated. Fetal predisposition to NAFLD involves numerous physiological reroutings that are initiated by increased delivery of nonesterified fatty acids to the fetal liver. Hampered β-oxidation, uncontrolled oxidative stress, increased triacylglycerol synthesis, and the endoplasmic reticulum unfolded protein response are all implicated in sculpting a hepatic phenotype with a propensity to develop NAFLD in the postnatal state. This review suggests a mechanism that integrates outcomes reported by a variety of studies conducted in an analysis of fetal hepatic metabolic capacity amid the maternal consumption of a high-fat diet. Potential preventive measures and therapies for use both as part of prenatal nutrition and for those at risk for the development of NAFLD are also discussed.

High-coverage metabolomics uncovers microbiota-driven biochemical landscape of interorgan transport and gut-brain communication in mice

“…For example, the methionine/glutathione transsulfuration pathway was extensively perturbed in brain, as characterized by elevated levels of L-methionine (1.47-fold), S-(5’-adenosyl)-L-homocysteine (SAH, 1.30-fold), L-glutathione (GSH, 15.1-fold), and 5’-deoxy-5’-methylthioadenosine (1.62-fold) when microbiota was present (Supplementary Fig. 3 ) 39 , 40 . We also noted for CONV-R brain elevated levels of two eicosanoids prostaglandin B2 (1.8-fold) and E2 (1.7-fold), α-ketoglutarate (AKG, 1.4-fold) (a sensitive oxidative stress indicator) as well as the antioxidative ketone body 3-hydroxybutyrate (2.0-fold).…”

Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis

“…The UPR functions to restore homeostasis by (1) upregulating chaperone proteins to assist with folding; (2) preventing the translation of non-UPR proteins; and (3) initiating apoptosis when resolution is unlikely. The UPR has a pathogenic role in several neurodegenerative diseases, type II diabetes, and non-alcoholic fatty liver disease [2], where signaling may contribute to the apoptosis of essential, mature cell types. However, unlike many of the cell types affected in such diseases, chondrocytes and osteoblasts undergo physiological UPR signaling in the course of normal maturation.…”

Alpha linolenic acid in maternal diet halts the lipid disarray due to saturated fatty acids in the liver of mice offspring at weaning

“…were suggested [ 2 ] to affect physiological and metabolic processes and the underlying genetic networks in tissue specific manner [ 3 , 4 ]. Increased biosynthesis and reduced oxidation of FAs triggers obesity development and obesity-related complications including insulin resistance (IR), and the metabolic syndrome [ 5 , 6 ]. High consumption of dietary fats also contributes to these diseases.…”