Relation Between Serum Free Fatty Acids and Adiposity, Insulin Resistance, and Cardiovascular Risk Factors From Adolescence to Adulthood

Frohnert, Brigitte I.; Jacobs, David R.; Steinberger, Julia; Moran, Antoinette; Steffen, Lyn M.; Sinaiko, Alan R.

doi:10.2337/db12-1122

Cited by 84 publications

(71 citation statements)

References 48 publications

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“…Changes likely coincide with the transition to a more adult body habitus and physiology during puberty. We previously demonstrated a continuation of this trend into young adulthood, by describing the correlations of CV risk factors between parents and older children during the transition from adolescence (mean age 15 years) to young adulthood (mean age 22 years); parent-child correlations become stronger over this interval (42). Thus, there appears to be a natural progression where the correlations between shared CV risk factors become more significant as young children transition through adolescence, and into adulthood.…”

Section: Discussionmentioning

confidence: 92%

Relation of Cardiometabolic Risk Factors between Parents and Children

Halvorsen

Moran

Jacobs

et al. 2015

The Journal of Pediatrics

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Objectives To explore the relations of parent-child cardiometabolic risk factors and assess the influence of adiposity on these associations. Study design Associations of adiposity, blood pressure, lipids, fasting insulin and glucose, and a risk factor cluster score were evaluated in a cross-sectional study of 179 parents and their children (6–18 years, N=255). Insulin resistance was assessed by euglycemic clamp in parents and children aged 10 or older. Metabolic syndrome in parents was defined by ATPIII criteria. Cluster scores of the risk factors were created based on age-specific z-scores. Analyses included Pearson correlation and linear regression, adjusted for parent and child age, sex, race, and body mass index (BMI), accounting for within-family correlation. Results We found positive parent-child correlations for measures of adiposity (BMI, BMI percentile, waist, subcutaneous fat, and visceral fat; r=0.22–0.34, all p≤0.003), systolic blood pressure (SBP) (r=0.20, p=0.002), total cholesterol (r=0.39, p<0.001), low-density lipoprotein cholesterol (r=0.34, p<0.001), high density lipoprotein cholesterol (r=0.26, p<0.001) triglycerides (r=0.19, p=0.01) and insulin sensitivity (r=0.22, p=0.02) as well as cluster scores (r=0.15, p=0.02). After adjustment for BMI all parent-child correlations, except systolic blood pressure, remained significant. Conclusions Although adiposity is strongly correlated between parents and children, many cardiometabolic risk factors correlate independent of parent and child BMI. Adverse parental cardiometabolic profiles may identify at-risk children independent of the child’s adiposity status.

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Section: Discussionmentioning

confidence: 92%

Relation of Cardiometabolic Risk Factors between Parents and Children

Halvorsen

Moran

Jacobs

et al. 2015

The Journal of Pediatrics

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“…Quantification of serum triglycerides similarly revealed no differences between T N and T S housing (Figure 1F). Notably, however, T N -housed ApoE −/− mice displayed significantly augmented levels of serum non-esterified fatty acids (NEFAs), a known marker and risk factor for atherosclerosis induction (Figure 1G) [29]. Quantification of lipid deposition in the aorta, via Oil Red O staining, revealed that WD fed, T N -housed ApoE −/− mice had significantly higher levels of aortic lipid accumulation (Figure 1H) and significantly larger atherosclerotic plaques (Figure 1I).…”

Section: Resultsmentioning

confidence: 99%

Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice

Giles

Ramkhelawon

Donelan

et al. 2016

Molecular Metabolism

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ObjectivesObesity and obesity-associated inflammation is central to a variety of end-organ sequelae including atherosclerosis, a leading cause of death worldwide. Although mouse models have provided important insights into the immunopathogenesis of various diseases, modeling atherosclerosis in mice has proven difficult. Specifically, wild-type (WT) mice are resistant to developing atherosclerosis, while commonly used genetically modified mouse models of atherosclerosis are poor mimics of human disease. The lack of a physiologically relevant experimental model of atherosclerosis has hindered the understanding of mechanisms regulating disease development and progression as well as the development of translational therapies. Recent evidence suggests that housing mice within their thermoneutral zone profoundly alters murine physiology, including both metabolic and immune processes. We hypothesized that thermoneutral housing would allow for augmentation of atherosclerosis induction and progression in mice.MethodsApoE−/− and WT mice were housed at either standard (TS) or thermoneutral (TN) temperatures and fed either a chow or obesogenic “Western” diet. Analysis included quantification of (i) obesity and obesity-associated downstream sequelae, (ii) the development and progression of atherosclerosis, and (iii) inflammatory gene expression pathways related to atherosclerosis.ResultsHousing mice at TN, in combination with an obesogenic “Western” diet, profoundly augmented obesity development, exacerbated atherosclerosis in ApoE−/− mice, and initiated atherosclerosis development in WT mice. This increased disease burden was associated with altered lipid profiles, including cholesterol levels and fractions, and increased aortic plaque size. In addition to the mild induction of atherosclerosis, we similarly observed increased levels of aortic and white adipose tissue inflammation and increased circulating immune cell expression of pathways related to adverse cardiovascular outcome.ConclusionsIn sum, our novel data in WT C57Bl/6 mice suggest that modulation of a single environmental variable, temperature, dramatically alters mouse physiology, metabolism, and inflammation, allowing for an improved mouse model of atherosclerosis. Thus, thermoneutral housing of mice shows promise in yielding a better understanding of the cellular and molecular pathways underlying the pathogenesis of diverse diseases.

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“…Moreover, the use of an HFD as an initial step in the T2DM rat model closely approximates human dietary habits over recent decades. It is well documented that elevated plasma FFA concentrations contribute to the significant inhibitory effects on insulin signaling . Increased plasma FFA concentrations (palmitic acid in particular) promote Cer synthesis by increasing the content of palmitoyl‐CoA, a precursor that dictates the rate of de novo Cer synthesis .…”

Section: Discussionmentioning

confidence: 99%