Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is heralded as the next big global epidemic. Hepatic de novo lipogenesis (DNL), the synthesis of new fatty acids from non-lipid sources, is thought to play a pivotal role in the development of NAFLD. While there is currently no NAFLD-specific therapeutic agent available, pharmaceutical drugs aimed at reducing hepatic fat accretion may prove to be a powerful ally in the treatment and management of this disease. With a focus on NAFLD, the present review summarizes current techniques examining DNL from a clinical perspective, and describes the merits and limitations of three commonly used assays; stable-label isotope tracer studies, fatty acid indexes and indirect calorimetry as non-invasive measures of hepatic DNL. Finally, the application of DNL assessments in the pharmacological and nutraceutical treatment of NAFLD/NASH is summarized. In a clinical research setting, measures of DNL are an important marker in the development of anti-NAFLD treatments.

Is non‐alcoholic fatty liver disease a reflection of what we eat or simply how much we eat?

“…As described above, the disaccharide, sucrose, which is a combination of fructose (50%) and glucose (50%), has been shown to significantly increase liver fat (as measured by MRI), at least when it is the main source of excess calories. When 47 overweight individuals were randomly assigned to consume one of the four different test drinks (1 L of sucrose‐sweetened regular cola and an equivalent amount of calories consumed as milk, aspartame‐sweetened diet cola, or water) daily for 6 months, the change in liver fat between baseline and 6 months was substantially higher in the sugar‐sweetened cola group compared with all other groups .…”

“…Carbohydrate overfeeding of an additional 1000 kcal per day from sugary drinks in 16 overweight participants (5 men and 11 women) rapidly increased liver fat content by 27% (as measured by magnetic resonance imaging [MRI]) over 3 weeks with a concurrent 2% increase in body weight . DNL (as measured by the lipogenic index) and very low‐density lipoprotein (VLDL) triglycerides were also increased in proportion to liver fat (ratios: 2.1 ± 0.3 compared with 3.2 ± 0.5; P < 0.05 and 2.1 [1.9–2.3] compared with 2.6 [2.4–4.1], P < 0.005, respectively) but only in those participants with a certain genotype (wild‐type genotype [PNPLA3‐148II]) of the patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) gene. A 6‐month hypocaloric diet reversed the weight and liver fat gain …”

Exacerbation of liver steatosis following exposure to famine and overnutrition

“…Using oil red O staining and HE staining, we found less serious liver steatosis in the famine‐NFD group as a result of attenuated DNL and HFD intake. Although the hepatic DNL in the famine‐NFD group was higher, and the liver accumulated more triglycerides than the NFD group, liver steatosis in the famine‐NFD group was not as serious as that in the famine‐HFD group .…”

Relation between plasma phospholipid oleic acid and risk of heart failure

“…Given the complexity and highly-regulated nature of endogenous production of fatty acids, there are undoubtedly numerous additional factors not yet studied affecting this process for which we currently cannot adjust in our measurements. Non-invasive techniques have been developed to determine levels of DNL in humans including stable isotope tracer studies, fatty acid profiling or indirect calorimetry [27] however, these techniques were not employed in the current study design.…”