Prolonged Caloric Restriction in Obese Patients With Type 2 Diabetes Mellitus Decreases Myocardial Triglyceride Content and Improves Myocardial Function Sebastiaan Hammer, Marieke Snel, Hildo J. ...Lamb, Ingrid M. Jazet, Rutger W. van der Meer, Hanno Pijl, Edo A. Meinders, Johannes A. Romijn, Albert de Roos, Johannes W. A. Smit In type 2 diabetes mellitus (T2DM), myocardial triglyceride (TG) stores are increased. We studied the effects of prolonged caloric restriction on myocardial TG content, myocardial function, and glucoregulation in obese patients with T2DM. Caloric restriction decreased body weight associated with improved glucoregulation, a decrease in myocardial TG content, and improvements in diastolic function. We conclude that myocardial TG stores in obese patients with T2DM are flexible and amendable to therapeutic intervention by caloric restriction. Therefore, the data emphasize the potential relevance of measuring myocardial TG content as a surrogate marker to assess the effects of metabolic interventions on the heart.
Background Cold exposure and β3-adrenergic receptor agonism, which both activate brown adipose tissue, markedly influence lipoprotein metabolism by enhancing lipoprotein lipase–mediated catabolism of ...triglyceride-rich lipoproteins and increasing plasma high-density lipoprotein (HDL) levels and functionality in mice. However, the effect of short-term cooling on human lipid and lipoprotein metabolism remained largely elusive. Objective The objective was to assess the effect of short-term cooling on the serum lipoprotein profile and HDL functionality in men. Methods Body mass index–matched young, lean men were exposed to a personalized cooling protocol for 2 hours. Before and after cooling, serum samples were collected for analysis of lipids and lipoprotein composition by1 H-nuclear magnetic resonance. Adenosine triphosphate–binding cassette A1 (ABCA1)-mediated cholesterol efflux capacity of HDL was measured using 3 Hcholesterol-loaded ABCA1-transfected Chinese hamster ovary cells. Results Short-term cooling increased serum levels of free fatty acids, triglycerides, and cholesterol. Cooling increased the concentration of large very low–density lipoprotein (VLDL) particles accompanied by increased mean size of VLDL particles. In addition, cooling enhanced the concentration of small LDL and small HDL particles as well as the cholesterol levels within these particles. The increase in small HDL was accompanied by increased ABCA1-dependent cholesterol efflux in vitro. Conclusions Our data show that short-term cooling increases the concentration of large VLDL particles and increases the generation of small LDL and HDL particles. We interpret that cooling increases VLDL production and turnover, which results in formation of surface remnants that form small HDL particles that attract cellular cholesterol.
Individuals of south Asian origin have a very high risk of developing type 2 diabetes compared with white Caucasians. We aimed to assess volume and activity of brown adipose tissue (BAT), which is ...thought to have a role in energy metabolism by combusting fatty acids and glucose to produce heat and might contribute to the difference in incidence of type 2 diabetes between ethnic groups.
We enrolled Dutch nationals with south Asian ancestry and matched Caucasian participants at The Rijnland Hospital (Leiderdorp, Netherlands). Eligible participants were healthy lean men aged 18-28 years, and we matched groups for BMI. We measured BAT volume and activity with cold-induced (18)F-fluorodeoxyglucose ((18)F-FDG) PET CT scans, and assessed resting energy expenditure, non-shivering thermogenesis, and serum parameters. This study is registered with the Netherlands Trial Register, number 2473.
Between March 1, 2013, and June 1, 2013, we enrolled 12 participants in each group; one Caucasian participant developed hyperventilation after (18)F-FDG administration, and was excluded from all cold-induced and BAT measurements. Compared with Caucasian participants, south Asian participants did not differ in age (mean 23.6 years SD 2.8 for south Asians vs 24.6 years 2.8 for Caucasians) or BMI (21.5 kg/m(2) 2.0 vs 22.0 kg/m(2) 1.6), but were shorter (1.74 m 0.06 vs 1.85 m 0.04) and lighter (65.0 kg 8.5 vs 75.1 kg 7.2). Thermoneutral resting energy expenditure was 1297 kcal per day (SD 123) in south Asian participants compared with 1689 kcal per day (193) in white Caucasian participants (difference -32%, p=0.0008). On cold exposure, shiver temperature of south Asians was 2.0°C higher than Caucasians (p=0.0067) and non-shivering thermogenesis was increased by 20% in white Caucasians (p<0.0001) but was not increased in south Asians. Although the maximum and mean standardised uptake values of (18)F-FDG in BAT did not differ between groups, total BAT volume was lower in south Asians (188 mL SD 81) than it was in Caucasians (287 mL 169; difference -34%, p=0.04). Overall, BAT volume correlated positively with basal resting energy expenditure in all assessable individuals (β=0.44, p=0.04).
Lower resting energy expenditure, non-shivering thermogenesis, and BAT volumes in south Asian populations might underlie their high susceptibility to metabolic disturbances, such as obesity and type 2 diabetes. Development of strategies to increase BAT volume and activity might help prevent and treat such disorders, particularly in south Asian individuals.
Dutch Heart Foundation (2009T038) and Dutch Diabetes Research Foundation (2012.11.1500).
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