Nellemann, Birgitte

AbstractContext:Lipoprotein lipase (LPL) activity is considered the rate-limiting step of very-low-density-lipoprotein triglycerides (VLDL-TG) tissue storage, and has been suggested to relate to the development of obesity as well as insulin resistance and type 2 diabetes.Objective:The objective of the study was to assess the relationship between the quantitative storage of VLDL-TG fatty acids and LPL activity and other storage factors in muscle and adipose tissue. In addition, we examine whether such relations were influenced by type 2 diabetes.Design:We recruited 23 men (12 with type 2 diabetes, 11 nondiabetic) matched for age and body mass index. Postabsorptive VLDL-TG muscle and subcutaneous adipose tissue (abdominal and leg) quantitative storage was measured using tissue biopsies in combination with a primed-constant infusion of ex vivo triolein labeled [1-14C]VLDL-TG and a bolus infusion of ex vivo triolein labeled [9,10-3H]VLDL-TG. Biopsies were analyzed for LPL activity and cellular storage factors.Results:VLDL-TG storage rate was significantly greater in men with type 2 diabetes compared with nondiabetic men in muscle tissue (P = 0.02). We found no significant relationship between VLDL-TG storage rate and LPL activity or other storage factors in muscle or adipose tissue. However, LPL activity correlated with fractional VLDL-TG storage in abdominal fat (P = 0.04).Conclusions:Men with type 2 diabetes have increased VLDL-TG storage in muscle tissue, potentially contributing to increased intramyocellular triglyceride and ectopic lipid deposition. Neither muscle nor adipose tissue storage rates were related to LPL activity. This argues against LPL as a rate-limiting step in the postabsorptive quantitative storage of VLDL-TG.

Direct FFA storage in adipose tissue is a recently appreciated pathway for postabsorptive lipid storage. We evaluated the effect of body fat distribution on direct FFA storage in women with different obesity phenotypes. Twenty-eight women [10 upper body overweight/obese (UBO; WHR >0.85, BMI >28 kg/m2), 11 lower body overweight/obese (LBO; WHR <0.80, BMI >28 kg/m2), and 7 lean (BMI <25 kg/m2)] received an intravenous bolus dose of [9,10-3H]palmitate- and [1-14C]triolein-labeled VLDL tracer followed by upper body subcutaneous (UBSQ) and lower body subcutaneous (LBSQ) fat biopsies. Regional fat mass was assessed by combining DEXA and CT scanning. We report greater fractional storage of FFA in UBSQ fat in UBO women compared with lean women ( P < 0.01). The LBO women had greater storage per 106fat cells in LBSQ adipocytes compared with UBSQ adipocytes ( P = 0.04), whereas the other groups had comparable storage in UBSQ and LBSQ adipocytes. Fractional FFA storage was significantly associated with fractional VLDL-TG storage in both UBSQ ( P < 0.01) and LBSQ ( P = 0.03) adipose tissue. In conclusion, UBO women store a greater proportion of FFA in the UBSQ depot compared with lean women. In addition, LBO women store FFA more efficiently in LBSQ fat cells compared with UBSQ fat cells, which may play a role in development of their LBO phenotype. Finally, direct FFA storage and VLDL-TG fatty acid storage are correlated, indicating they may share a common rate-limiting pathway for fatty acid storage in adipose tissue.