Nutritional regulation of hepatic de novo lipogenesis in humans

Abstract

Purpose of reviewDe novo lipogenesis (DNL) is a metabolic process occurring mainly within the liver, in humans. Insulin is a primary signal for promoting DNL; thus, nutritional state is a key determinant for upregulation of the pathway. However, the effects of dietary macronutrient composition on hepatic DNL remain unclear. Nor is it clear if a nutrition-induced increase in DNL results in accumulation of intra-hepatic triglyceride (IHTG); a mechanism often proposed for pathological IHTG. Here, we review the latest evidence surrounding the nutritional regulation of hepatic DNL.Recent findingsThe role of carbohydrate intake on hepatic DNL regulation has been well studied, with only limited data on the effects of fats and proteins. Overall, increasing carbohydrate intake typically results in an upregulation of DNL, with fructose being more lipogenic than glucose. For fat, it appears that an increased intake of n-3 polyunsaturated fatty acids downregulates DNL, whilst, in contrast, an increased dietary protein intake may upregulate DNL.SummaryAlthough DNL is upregulated with high-carbohydrate or mixed-macronutrient meal consumption, the effects of fat and protein remain unclear. Additionally, the effects of different phenotypes (including sex, age, ethnicity, and menopause status) in combination with different diets (enriched in different macronutrients) on hepatic DNL requires elucidation.

Semaglutide Improves Liver Steatosis and De Novo Lipogenesis Markers in Obese and Type-2-Diabetic Mice with Metabolic-Dysfunction-Associated Steatotic Liver Disease

“…Elevated hepatic de novo lipogenesis, a process in which the liver synthesizes fatty acids from dietary carbohydrates and proteins, is among the earliest metabolic abnormalities related to insulin resistance and fatty liver disease [ 35 ]. In this context, we observed that semaglutide led to a reduction in intrahepatic TG content and de novo lipogenesis, as evidenced by decreased levels of de novo lipogenesis end products, such as lipotoxic fatty acids (palmitic, palmitoleic and oleic acids) and the downregulation of lipogenic enzymes (Acaca, Fasn and Scd1).…”

The Replacement of Only One Portion of Starchy Carbohydrates with Green Leafy Vegetables Regresses Mid and Advanced Stages of NAFLD: Results from a Prospective Pilot Study

“…In particular, the replacement of a daily carbohydrate portion with 200 gr of brassicaceous vegetables improves the circulating biomarkers linked to NAFLD, the FLI, and the FibroScan score. These results are explained by sugar restriction, which both downregulate the de novo lipogenesis (DNL) widely recognized in NAFLD [ 28 , 29 ] and reduce inflammatory responses [ 30 ]. Furthermore, our findings support recent research showing an inverse relationship between leafy green vegetable consumption and NAFLD [ 31 ].…”

Editorial: Lipids to support physiology and function: both quantity and quality are important

“…Inclusion of fish oil has been shown to both prevent and reverse IFALD in premature infants [45], and in some reports to improve IFALD in adults. These effects may relate to the impact of long chain n-3 PUFAs on hepatic lipid metabolism as also discussed by Cross et al [2].…”

“…Despite decades of research, much remains to be learned about fatty acid and complex lipid metabolism in humans and its regulation. Cross et al [2] provide an update on regulation of de novo lipogenesis (DNL; synthesis of fatty acids and their accumulation into triglycerides) which mainly occurs in the liver. They also review the experimental techniques that can be used to assess DNL in humans.…”