Background and aims: Hepatic steatosis may contribute to poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. As saturated fatty acids (SFA) are the product of DNL, the hepatic SFA fraction may be a marker of DNL and contribute to insulin resistance. Using novel MR methodology, we were able to distinguish the fractions of hepatic saturated, mono- and polyunsaturated fatty acids (SFA, MUFA and PUFA, respectively) in vivo. Here, we investigated the association between DNL, in vivo hepatic lipid content and composition, and hepatic insulin sensitivity (IS).

Materials and methods: In eighteen healthy overweight/obese participants (BMI 29.6±2.2 kg/m2; age 58.7±7.0 year; 10 women) with a wide range in liver fat content (1-40%), we determined liver fat content and composition (fraction of SFA, MUFA, PUFA relative to total amount) using 1H-MRS, DNL by deuterated water and hepatic IS using the low-dose phase (10 mU/m2/min) of a 2-step hyperinsulinemic-euglycemic clamp. SFA fraction was also determined in specific patient populations with either high DNL (glycogen storage disease type 1a patients, n=7) or low hepatic insulin sensitivity (type 2 diabetes patients, n=9).

Results: DNL was strongly associated with SFA fraction (r=+0.52, p=0.047) and negatively with MUFA fraction (r=-0.70, p=0.003), but not with PUFA fraction or total liver fat content in overweight/obese volunteers. In glycogen storage disease type 1a patients, SFA fraction was higher compared with overweight/obese participants with comparable hepatic fat content (49.5±2.0 and 42.9±0.8 %, p=0.031. Interestingly, higher SFA fraction was associated with lower hepatic IS (% insulin-suppressed endogenous glucose production) in obese/overweight participants (r=-0.53 p=0.016). Total liver fat content, MUFA and PUFA fraction were not associated with hepatic IS. The association between high SFA and low hepatic IS was confirmed in patients with type 2 diabetes, characterised by low hepatic IS, showing increased SFA fraction compared with overweight/obese participants (42.8±1.3 and 35.5±3.1 %, p=0.024). 

Conclusions: These results show that the hepatic SFA fraction, as determined by 1H-MRS, might be used as measure of DNL. Furthermore, the results suggest that specifically the hepatic SFA fraction contributes to hepatic insulin resistance.

05 - HEPATIC SATURATED FATTY ACID FRACTION IS ASSOCIATED WITH DE NOVO LIPOGENESIS AND HEPATIC INSULIN SENSITIVITY IN OVERWEIGHT AND OBESE SUBJECTS