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Background and Aims: Insulin resistance is considered an indicator of the severity of MASLD. In this context, the role of skeletal muscle fat and its intra- or extra-myocellular localisation on insulin sensitivity remains debated. The aim of this study is to assess muscle lipid content and cellular localisation using proton-magnetic resonance spectroscopy (1H-MRS) and its relationship with insulin resistance in a cohort of MASLD subjects. Method: MASLD patients were prospectively recruited based on the co-existence of liver steatosis measured by a controlled attenuation-parameter (CAP) above 251 dB/m and at least one cardiometabolic risk factor. Type 2 diabetes was defined by the intake of hypoglycemic drugs. Insulin resistance was estimated in non-diabetic patients using the homeostatic model assessment of insulin resistance (HOMA-IR). Intra (IMCL) and extramyocellular lipids (EMCL) were measured in vivo using 1H-MRS. Single voxel 1H-MRS was performed on a 3-Tesla Signa Premier scanner (GE healthcare) on tibialis anterior (TA) and soleus using a PRESS-sequence (voxel size 10 X 10 X 15 mm3, TE=27ms, TR=1500ms, 8 averages). JMRUI software, including the AMARES algorithm was used to quantify IMCL and EMCL on non-water suppressed spectra. Results: 54 MASLD patients were included. 32 patients were male (59%), with a mean age of 54 years (range: 19-75). 27 patients were diabetic (50%). Mean BMI was 35 (range: 24-60). Mean waist circumference was 118 cm (range: 89-160). Mean CAP and liver elasticity were 342 dB/m (range: 242-400) and 14.8 kPa (range: 3.6-35). In the entire cohort, mean TA lipid content was 0.6% for IMCL (range: 0.1-1.5) and 1.8% (0.3-6.8) for EMCL (p < 0.05). Mean soleus lipid content was 0.8% for IMCL (range: 0.2-2.1) and 4.4% for EMCL (range: 0.3-10.9) (p < 0.05). In non-diabetic patients, mean fasting glycaemia was 103 mg/dl (range: 76-126) and mean HOMA-IR was 8 (range: 1.7-26). The HOMA-IR index was positively correlated to IMCL content in the TA (r = 0.63, p = 0.017) but no correlation was found with EMCL content or with soleus fat content (IMCL and EMCL). Diabetic patients had a higher IMCL content in the soleus compared to non-diabetic patients (0.9% versus 0.6%; p = 0.02). No difference was highlighted for the EMCL content of soleus (4.1% in diabetic subjects versus 4.7%; p > 0.05) or for IMCL for TA between diabetic and non-diabetic patients (0.55% versus 0.7%; p > 0.05). Conclusion: The majority of skeletal muscle lipids are extramyocellular. However, IMCL but not EMCL content assessed by 1H-MRS positively correlates with insulin resistance assessed by the HOMA-IR index in non-diabetic MASLD patients. This observation is reinforced by the IMCL content in diabetic patients being significantly higher compared to non-diabetic patients. This observation highlights a link between IMCL, systemic insulin resistance and type 2 diabetes in MASLD.
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Henin, G., Nachit, M., Reyngoudt, H., Danse, E., Trefois, P., Peeters, F., Declerck, S., André-Dumont, S., Goffaux, A., Marty, B., Leclercq, I., Loumaye, A., & Lanthier, N. (2024). Intramyocellular lipids are associated with insulin resistance in metabolic dysfunction-associated steatotic liver disease. Journal of Hepatology, 80(S1), S473-S474. https://doi.org/10.1016/s0168-8278(24)01457-0 (Original work published 2024)