Abstract Background Elevated stearoyl-CoA desaturase activity has been described in obese states, with an increased desaturation index (DI) suggesting enhanced lipogenesis. Differences in the DI among various phenotypes of abnormal adiposity have not been studied. Abnormal accumulation of subcutaneous adipose tissue occurs in rare adipose disorders (RADs) including Dercum's disease (DD), multiple symmetric lipomatosis (MSL), and familial multiple lipomatosis (FML). Examining the DI in subcutaneous fat of people with DD, MSL and FML may provide information on adipose tissue fatty acid metabolism in these disorders. The aims of this pilot study were: 1) to determine if differences in adipose tissue DIs are present among RADs, and 2) to determine if the DIs correlate to clinical or biochemical parameters. Methods Subcutaneous adipose tissue was obtained from human participants with DD (n = 6), MSL (n = 5), FML (n = 8) and obese Controls (n = 6). Fatty acid composition was determined by gas chromatography/mass spectrometry. The DIs (palmitoleic/palmitic, oleic/stearic, vaccenic/stearic ratios) were calculated from the gas chromatogram peak intensities. SCD1 gene expression was determined. Spearman's correlations between the DIs and available clinical or biochemical data were performed. Results In DD subjects, the vaccenic/stearic index was lower (p < 0.05) in comparison to Controls. Percent of total of the saturated fatty acid myristic acid was higher in DD compared with Controls and FML. Percent of monounsaturated vaccenic acid in DD trended lower when compared with Controls, and was decreased in comparison to FML. In MSL, total percent of the polyunsaturated fatty acids was significantly lower than in the Control group (p < 0.05). In the total cohort of subjects, the palmitoleic/palmitic and oleic/stearic DIs positively correlated with age, BMI, and percent body fat. Conclusions The positive associations between the DIs and measures of adiposity (BMI and percent body fat) support increased desaturase activity in obesity. The lower vaccenic/stearic DI in DD SAT compared with Controls suggests presence of other factors involved in fat accumulation in addition to lifestyle. Other mechanisms driving fat accumulation in DD such as inflammation or lymphatic dysfunction should be investigated.

Lactate dehydrogenase A (LDHA) is the enzyme that converts pyruvate to lactate and oxidizes the reduced form of nicotinamide adenine dinucleotide (NADH) to NAD⁺. Several human cancers including the pancreas display elevated expression of LDHA. Because of its essential role in cancer metabolism, LDHA has been considered to be a potential target for cancer therapy. Recently, we have shown that a green tea extract significantly down-regulated LDHA in HPAF-II pancreatic cancer cells using global proteomics profiling. The present study is to investigate how EGCG, a major biological active constituent of green tea, targets the metabolism of human pancreatic adenocarcinoma MIA PaCa-2 cells. We compared the effect of EGCG to that of oxamate, an inhibitor of LDHA, on the multiple metabolic pathways as measured by extracellular lactate production, glucose consumption, as well as intracellular aspartate and glutamate production, fatty acid synthesis, acetyl-CoA, RNA ribose and deoxyribose. Specific metabolic pathways were studied using [1, 2-¹³C₂]-d-glucose as the single precursor metabolic tracer. Isotope incorporations in metabolites were analyzed using gas chromatography/mass spectrometry (GC/MS) and stable isotope-based dynamic metabolic profiling (SiDMAP). We found that the EGCG treatment of MIA PaCa-2 cells significantly reduced lactate production, anaerobic glycolysis, glucose consumption and glycolytic rate that are comparable to the inhibition of LDHA by oxamate treatment. Significant changes in intracellular glucose carbon re-distribution among major glucose-utilizing macromolecule biosynthesis pathways in response to EGCG and oxamate treatment were observed. The inhibition of LDHA by EGCG or oxamate impacts on various pathways of the cellular metabolic network and significantly modifies the cancer metabolic phenotype. These results suggest that phytochemical EGCG and LDHA inhibitor oxamate confer their anti-cancer activities by disrupting the balance of flux throughout the cellular metabolic network.

Abstract Background Small for gestational age (SGA) leads to increased risk of adult obesity and metabolic syndrome. Offspring exposed to 50% maternal food restriction in utero are born smaller than Controls (FR), catch-up in growth by the end of the nursing period, and become obese adults. The objective of the study was to determine stearoyl-CoA desaturase activity (SCD1) and rates of de novo fatty acid synthesis in young FR and Control offspring tissues at the end of the nursing period, as possible contributors to catch-up growth. Methods From gestational day 10 to term, dams fed ad libitum (Control) or were 50% food-restricted to produce small FR pups. Control dams nursed all pups. At postnatal day 1 (p1) and p21, offspring body tissues were analyzed by GC/MS, and desaturation indices of palmitoleate/palmitate and oleate/stearate were calculated. SCD1 gene expression was determined by real-time PCR on adipose and liver. Offspring were enriched with deuterium that was given to dams in drinking water during lactation and de novo synthesis of offspring body tissues was determined at p21. Primary adipocyte cell cultures were established at p21 and exposed to U13C-glucose. Results FR offspring exhibited higher desaturation index in p1 and p21 adipose tissue, but decreased desaturation index in liver at p21. SCD1 gene expression at p21 was correspondingly increased in adipose and decreased in liver. FR subcutaneous fat demonstrated increased de novo synthesis at p21. Primary cell cultures exhibited increased de novo synthesis in FR. Conclusions Adipose tissue is the first site to exhibit increased de novo synthesis and desaturase activity in FR. Therefore, abnormal lipogenesis is already present prior to onset of obesity during the period of catch-up growth. These abnormalities may contribute to future obesity development.

In offspring exposed in utero to a maternal diet high in fat (HF), we have previously demonstrated that despite similar birth weights, HF adult offspring at 6 months of age had significantly higher body weights, greater adiposity, and increased triacylglycerol (TAG) levels as compared to controls. We hypothesized that a maternal HF diet predisposes to offspring adiposity via a programmed increase in the synthesis of monounsaturated fatty acids in the liver and hence increased substrate availability for liver TAG synthesis. We further hypothesized that programmed changes in offspring liver fatty acid metabolism are associated with increased liver expression of the lipogenic enzyme stearoyl-CoA desaturase-1 (SCD-1). Female rats were maintained on a HF diet rich in monounsaturated fatty acids (MUFA) prior to and throughout pregnancy and lactation. After birth, newborns were nursed by the same dam, and all offspring were weaned to control diet. Plasma and liver fatty acid compositions were determined using gas chromatography/mass spectrometry. Fatty acid C16 desaturation indices of palmitoleic/palmitic and (vaccenic + palmitoleic)/palmitic and the C18 desaturation index of oleic/stearic were calculated. Liver protein abundance of SCD-1 was analyzed in newborns and adult offspring. Plasma and liver C16 desaturation indices were decreased in HF newborns, but increased in the adult offspring. Liver SCD-1 expression was increased in the HF adult offspring. These data show that the maternal HF diet during pregnancy and lactation increases offspring liver SCD-1 protein abundance and alters the liver C16 desaturase pathway.

Abstract Background Small-for-gestational age (SGA) at birth increases risk of development of adult obesity and insulin resistance. A model of SGA rat offspring has been shown to exhibit increased adipose tissue expression of a key adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), and increased fatty acid de novo synthesis during the nursing period, prior to onset of obesity. PPARγ agonists have been studied for potential use in the prevention of insulin resistance. Moreover, SGA adipocytes exhibit age-dependent differences in lipogenesis as mediated by PPARγ. The effects of PPARγ modulators on lipogenic gene expression and de novo lipogenesis on the age-dependent changes in SGA adipocytes are not known. The objectives of this study were: 1) to determine the adipogenic and lipogenic potential in SGA adipocytes at postnatal day 1 (p1) and day 21 (p21), 2) to determine how the PPARγ activator- and repressor-ligands affect the lipogenic potential, and 3) to determine the fatty acid metabolic response to PPARγ activator-ligand treatment. Methods Primary adipocyte cultures from p1 and p21 SGA and Control male offspring were established from a known maternal food-restriction model of SGA. Cell proliferation and Oil Red O (ORO) staining were quantified. Adipocytes were treated with increasing doses of rosiglitazone or bisphenol-A diglycidyl ether (BADGE). PPARγ and SREBP1 protein expression were determined. De novo lipogenesis with rosiglitazone treatment at p21 was studied using 50% U13C-glucose and gas chromatography/mass spectrometry. Results At p1 and p21, SGA demonstrated increased cell proliferation and increased ORO staining. At p21, SGA demonstrated increased lipogenic gene expression and increased glucose-mediated fatty acid de novo synthesis compared with Controls. In response to rosiglitazone, SGA adipocytes further increased glucose utilization for fatty acid synthesis. SGA lipogenic gene expression demonstrated resistance to BADGE treatment. Conclusions SGA adipocytes exhibit an enhanced adipogenic and lipogenic potential in early postnatal life. By p21, SGA demonstrated resistance to PPARγ repressor-ligand treatment, and selective response to high dose PPARγ activator-ligand treatment in adipogenic and lipogenic gene expression. p21 SGA adipocytes revealed increased fatty acid de novo synthesis through a complex relationship with glucose metabolism.

Objective

This study aims to describe differences in health care utilization between homeless and nonhomeless minors with diabetes.

Research design and methods

Data from the Healthcare Cost and Utilization Project's Statewide Inpatient Database from New York for years 2009-2014 were examined to identify pediatric patients <18 years old with diabetes. Outcomes of interest included hospitalization rate, in-hospital mortality, admission through the emergency department (ED), diabetic ketoacidosis (DKA), hospitalization cost, and length of stay (LOS). Other variables of interest included age-group, race/ethnicity, insurance type, and year. Multivariate logistic regression models were used for in-hospital mortality, admission through ED, and DKA. Log-transformed linear regression models were used for hospitalization cost, and negative binomial regression models were used for LOS.

Results

A total of 643 homeless and 10,559 nonhomeless patients were identified. The hospitalization rate was higher among homeless minors, with 3.64 per 1,000 homeless population compared with 0.38 per 1,000 in the nonhomeless population. A statistically significant higher readmission rate was detected among homeless minors (20.4% among homeless and 14.1% among nonhomeless, P < 0.01). Lower rates of DKA (odds ratio 0.75, P = 0.02), lower hospitalization costs (point estimate 0.88, P < 0.01), and longer LOS (incidence rate ratio 1.20, P < 0.01) were detected among homeless minors compared with nonhomeless minors.

Conclusions

This study found that among minors with diabetes, those who are homeless experience a higher hospitalization rate than the nonhomeless. Housing instability, among other environmental factors, may be targeted for intervention to improve health outcomes.

Objective

This randomized clinical trial tested the effectiveness of an addiction-based digital weight-loss intervention, focusing on withdrawal/abstinence from self-identified problem foods, snacking and excessive amounts at meals, and discomfort displacement, with and without coaching, compared to an in-person, multi-disciplinary, care model among adolescents with obesity. We hypothesized that the digital intervention with coaching would yield greater weight loss and lower delivery burden than the standard clinical arm, and greater participant engagement than the digital arm without coaching.

Methods

Adolescents were randomized to app intervention, with or without coaching, or in-person multidisciplinary obesity intervention for 6 months. The primary outcome was change in %BMI_p95 at weeks 12 and 24. A mixed-effects linear regression model was used to assess the association between change in %BMI_p95 and intervention arm. We were also interested in assessing delivery burden, participant engagement and evaluating the relationships between weight change and demographic characteristics, mood, executive function and eating behaviours.

Results

All adolescents (n = 161; BMI ≥95th%, age 16 ± 2.5 year; 47% Hispanic, 65% female, 59% publicly insured) lost weight over 24-weeks (-1.29%, [-1.82, -0.76], p < 0.0001), with no significant weight loss difference between groups (p = 0.3). Girls lost more weight than boys, whereas binge eating behaviour at baseline was associated with increase in %BMI_p95 when controlling for other covariates. There was no association between ethnicity, mood, timing of intervention in relation to the pandemic, or executive function and change in %BMI_p95 .

Conclusions

Contrary with our hypothesis, our results showed no difference in the change in BMI status between treatment arms. Since efficacy of this digital intervention was not inferior to in-person, multi-disciplinary care, this could offer a reasonable weight management option for clinicians, based on youth and family specific characteristics, such as accessibility, resources, and communication styles.

Clinical trial registration

ClinicalTrials.gov identifier: NCT035008353.

In South Los Angeles, a community-engaged research project on obesity was initiated between a translational research institute seeking to build community-based or partnered participatory research (CBPR/CPPR) capacity, and a community partner with extensive experience. This manuscript describes the partnership-building process and discusses results from a bi-directional knowledge transfer event.