Personalized weight loss programs in obese children are shown to reduce specific harmful lipids linked to heart disease and metabolic issues, offering a promising strategy for early intervention and long-term health benefits.
Study: Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity. Image Credit: Pixel-Shot / Shutterstock.com
A recent study published in the journal Nature Medicine assesses the lipid profiles of obese children and adolescents and their health implications.
What is obesity?
Obesity refers to the abnormal accumulation of fat in the body. Both genetic and acquired traits contribute to the etiology of obesity, with some studies suggesting that up to 67% of obesity is heritable.
Obesity in children may increase the risk of developing diabetes or prediabetes, hypertension, and metabolic dysfunction-associated steatotic liver disease (MASLD), the latter of which is present in 40% of obese children. Furthermore, obesity affects the lipidome, with higher total cholesterol (TC), low-density lipoprotein (LDL), and triglyceride (TG) levels often observed, in addition to lower healthy high-density lipoprotein (HDL) levels.
The current study examined how lipid profiles and individual lipid levels among obese children and adolescents impacted their health, with a specific focus on insulin resistance, dyslipidemia, fatty liver, and cardiometabolic risk factors.
About the study
The researchers conducted a lipid profile test on 958 children and adolescents who were either overweight or obese (OO). They compared these results to 373 children and adolescents of normal weight (NW) from the HOLBAEK study. Lipid levels were also measured in a subset of 186 children and adolescents who underwent a personalized non-pharmacological weight management program called the Holbaek obesity treatment.
The OO group had increased measures of body fat mass and liver fat percentage, elevated liver enzymes, including alanine transaminase (ALT), aspartate transaminase (AST), and γ-glutamyl transferase (GGT), and higher LDL, TG, and TC levels. Glucose, insulin, and C-peptide levels, with the homeostasis model assessment of insulin resistance (HOMA-IR), were also raised, thus indicating glycemic dysregulation.
Markers of dysregulated appetite, satiety, and systemic inflammation were also observed. Fatty liver was more common in the OO group.
In 15.6% of the OO group, liver fat comprised 5% or more of the liver as compared to 0% in the NW group. Elevated ALT levels and dyslipidemia were present in 38.7% and 38% of the OO group, compared to 12.6% and 10.8%, respectively, in the NW group.
Hyperglycemia, insulin resistance, and hypertension were more common in the OO group at 14%, 35%, and 15.9%, respectively, compared to 8.6%, 5.6%, and 3% in the NW group.
Lipids associated with obesity/overweight
A total of 121 lipids were differentiated between the NW and obese groups, 43 between the overweight and NW groups, and 60 between the overweight and obese groups. 52 and 35 lipids had positive and negative associations with obesity, respectively.
Large proportions of ceramides, TGs, fatty acids, and all diacylglycerols were positively linked to obesity. Conversely, most glycerophospholipids, such as phosphatidylethanolamines (PEs) and lysophosphatidylcholine (LPC), were inversely correlated. With phosphatidylcholine (PC), PE, and phosphatidylinositols (PIs), negative and positive correlations with obesity were observed.
As age increased, NW children exhibited higher lysophospholipid levels than those in the OO group.
Lipids predict cardiometabolic disease
The OO group had higher ceramide levels and reduced lysophospholipids and omega-3 fatty acid levels. Ceramides and other sphingolipids, PE, and PIs predicted insulin resistance and cardiometabolic risk; however, sphingomyelins (SM) were associated with an inverse correlation.
Ceramide production in the body requires SM and fatty acids. Low SM levels are associated with inflammation, and ceramide levels are associated with future cardiovascular disease (CVD) risk. PE and PI have been associated with the development of type 2 diabetes, fatty liver disease, and CVDs.
Both liver enzymes and a three-lipid panel of PI, PE, and ceramides provided similar predictive ability for hepatic steatosis. When both factors were integrated, the prediction accuracy was 82%.
The association of cardiometabolic traits with obesity was partly due to lipid abnormalities, especially PC and TG. However, SM, LPE, and LPC were inverse mediators of this association.
Weight reduction
Of the 186 children in the weight management program, 154 successfully lost weight and body fat percentage, exhibiting reduced total and LDL cholesterol, blood pressure, and glycated hemoglobin levels.
The weight management plan significantly reduced levels of ceramides, SM, PE, and PI species, and triglycerides. These changes reduced cardiometabolic risk by 23%.
Conclusions
The current study identified several lipids, including ceramides and large TG, that contribute to the future risk of CVDs and other metabolic diseases among overweight and obese children. This observation suggests these lipid classes disrupt normal homeostasis and metabolic pathways before adulthood.
Moreover, obesity management reduced specific lipid species, including ceramides, TG, PE, and PI. Thus, personalized obesity reduction programs are crucial to monitor healthy lipid profiles, particularly for children and adolescents.
Journal reference:
- Huang, Y., Sulek, K., Stinson, S. E., et al. (2024). Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity. Nature Medicine. doi:10.1038/s41591-024-03279-x.