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The Journal of Clinical Endocrinology... Jun 2024The renin-angiotensin-aldosterone system (RAAS) and adiposity measures are independently associated with the development of diabetes in African American (AA) adults....
BACKGROUND
The renin-angiotensin-aldosterone system (RAAS) and adiposity measures are independently associated with the development of diabetes in African American (AA) adults. However, studies have not examined the combined interaction between RAAS and adiposity measures in relation to diabetes risk in AA adults.
OBJECTIVE
We examined the longitudinal association of combined RAAS and adiposity measures with incident diabetes among AAs in the Jackson Heart Study.
METHODS
AA adults were assessed at baseline (2000-2004) and over 12 years of follow-up. RAAS, anthropometric (waist circumference [WC], body mass index [BMI]) and adipokine (adiponectin, leptin, leptin: adiponectin ratio [LAR]) measures were collected at baseline. Aldosterone, WC, and LAR were chosen as the best predictor variables. The final model, adjusting for age, sex, education, occupation, systolic blood pressure, smoking, physical activity and RAAS altering medications, incorporated these variables and their interactions (WC*Aldosterone + LAR*Aldosterone) to explore their impact on incident diabetes.
RESULTS
Among 3,220 participants without diabetes at baseline, there were 554 incident cases over a median follow-up of 7.5 years. Aldosterone, WC, and LAR were positively associated with incident diabetes (all p < 0.05). A significant interaction was found between WC and aldosterone with a greater association among individuals with lower WC. This interaction was significant in participants with prediabetes but not in those with normoglycemia. No significant interaction was found between log-LAR and aldosterone with risk of incident diabetes.
CONCLUSION
Higher aldosterone in participants is associated with greater risk of diabetes, particularly among individuals with prediabetes and lower WC.
PubMed: 38885313
DOI: 10.1210/clinem/dgae396 -
Frontiers in Veterinary Science 2024In older horses, basal metabolic rate decreases, and plasma metabolite and hormone concentrations related to energy metabolism change. The occurrence of age-related...
In older horses, basal metabolic rate decreases, and plasma metabolite and hormone concentrations related to energy metabolism change. The occurrence of age-related diseases, which increases in old animals, may enhance inflammatory reactivity (inflammaging). Finding the appropriate treatment for inflammaging at an early stage may prevent various age-related diseases. Changes in metabolite and hormone concentrations and enzyme activities involved in energy metabolism in the plasma of clinically healthy riding horses of various ages were measured to identify biomarkers of inflammaging (persistent low-grade inflammation that occurs with aging). All horses were clinically healthy, and their body condition scores (BCSs) were 4 or 5 (9-point scale). Plasma triglyceride (TG), total cholesterol (T-Cho), blood urea nitrogen (BUN), insulin concentrations, malondialdehyde (MDA), and serum amyloid A (SAA) concentrations generally increased with age. Adiponectin concentrations, plasma superoxide dismutase (SOD), and leukocyte AMP-activated protein kinase (AMPK) activities decreased, while plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutathione peroxidase (GPx) remained unchanged as horses aged. Although riding horses that partake in continuous exercise seems to be less likely to develop inflammaging, horses over 17 years of age tend to show proinflammatory signs with disordered lipid metabolism. In riding horses, SAA, in combination with other markers, may be a useful biomarker for inflammaging and dysregulated lipid metabolism in aging horses.
PubMed: 38881783
DOI: 10.3389/fvets.2024.1345548 -
The Journal of Nutrition Jun 2024The incongruity between dietary patterns and the circadian clock poses an elevated risk for metabolic health issues, particularly obesity and associated metabolic...
BACKGROUND
The incongruity between dietary patterns and the circadian clock poses an elevated risk for metabolic health issues, particularly obesity and associated metabolic disorders. The intestinal microflora engages in regulating various physiological functions of the host through its metabolites.
OBJECTIVES
This study aimed to investigate the impact of reversed feeding schedules during the day and night on intestinal flora and lipid metabolism in high-fat diet-induced obese mice.
METHODS
Mice aged 8-10 wk were subjected to either daytime or nighttime feeding and were administered a control or high-fat diet for 18 wk. At the end of the experiment, various assessments were conducted, including analysis of serum biochemic indices, histologic examination, evaluation of gene and protein expression in adipose tissue, and scrutiny of changes in intestinal microbial composition.
RESULTS
The results showed that day-night reversed feeding caused an increase in fasting blood glucose and exacerbated the high-fat diet-induced weight gain and lipid abnormalities. The mRNA expression levels of Leptin and Dgat1 were increased by day-night reversed feeding, which also reduced the expression level of adiponectin under the high-fat diet. Additionally, there was a significant increase in the protein concentrations of PPARγ, SREBP1c, and CD36. Inverted feeding schedules led to a reduction in intestinal microbial diversity, an increase in the abundance of inflammation-related bacteria, such as Coriobacteriaceae_UCG-002, and a suppression of beneficial bacteria, including Akkermansia, Candidatus_Saccharimonas, Anaeroplasma, Bifidobacterium, Carnobacterium, and Odoribacter. Acinetobacter exhibited a significant negative correlation with Leptin and Fasn, suggesting potential involvement in the regulation of lipid metabolism.
CONCLUSIONS
The results elucidated the abnormalities of lipid metabolism and intestinal flora caused by day-night reversed feeding, which exacerbates the adverse effects of a high-fat diet on lipid metabolism and intestinal microflora. This reversal in feeding patterns may disrupt both intestinal and lipid metabolism homeostasis by altering the composition and abundance of intestinal microflora in mice.
PubMed: 38880175
DOI: 10.1016/j.tjnut.2024.06.004 -
Thyroid : Official Journal of the... Jul 2024Resistance to thyroid hormone beta (RTHβ) is a rare disease resulting from mutations in the gene, characterized by reduced T3 action in tissues with high thyroid...
Resistance to thyroid hormone beta (RTHβ) is a rare disease resulting from mutations in the gene, characterized by reduced T3 action in tissues with high thyroid hormone receptor β expression. Thyroid hormones regulate body composition and metabolism in general, and increased or decreased hormone levels are associated with insulin resistance. This study evaluated the presence of cardiometabolic risk factors and insulin sensitivity in patients with RTHβ. In all, 16 patients, 8 adults (52.3 ± 16.3 years of age) and 8 children (10.9 ± 3.9 years of age), were compared to 28 control individuals matched for age, sex, and body mass index (BMI). Anthropometry evaluation and blood samples were collected for glycemia, lipids, insulin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, adiponectin, ultrasensitive C-reactive protein (CRPus), free thyroxine, total triiodothyronine, thyrotropin, and anti-thyroid peroxidase measurements. Body composition was assessed using dual-emission X-ray absorptiometry and bioimpedance. Insulin sensitivity was evaluated in adult patients and controls using the hyperinsulinemic-euglycemic clamp (HEC), whereas homeostasis model assessment of insulin resistance (HOMA-IR) was calculated in all individuals studied. Patients and controls presented similar weight, BMI, abdominal perimeter, and total fat body mass. Patients with RTHβ demonstrated higher total cholesterol (TC), = 0.04, and low-density lipoprotein cholesterol (LDL-C), = 0.03, but no alteration was observed in other parameters associated with metabolic risk, such as leptin, TNF-α, and CRPus. Two adult patients met the criteria for metabolic syndrome. There was no evidence of insulin resistance assessed by HEC or HOMA-IR. Elevated IL-6 levels were observed in patients with RTHβ. Using HEC as the gold standard method, no evidence of reduced insulin sensitivity in skeletal muscle was documented in RTHβ adult patients; however, higher levels of TC and LDL-C were observed in these patients, which suggest the need for active monitoring of this abnormality to minimize cardiometabolic risk. In addition, we demonstrated, for the first time, that the increase in IL-6 levels in patients with RTHβ is probably secondary to metabolic causes as they have normal levels of TNF-α and CRPus, which may contribute to an increase in cardiovascular risk. A larger number of patients must be studied to confirm these results.
PubMed: 38877800
DOI: 10.1089/thy.2024.0132 -
Endocrine Practice : Official Journal... Jun 2024Data is scant on impact of metformin use in gestational diabetes (GDM)/ diabetes in pregnancy (DIP) on long-term outcomes in children and mothers beyond 5-years of... (Review)
Review
BACKGROUND
Data is scant on impact of metformin use in gestational diabetes (GDM)/ diabetes in pregnancy (DIP) on long-term outcomes in children and mothers beyond 5-years of child-birth. This systematic-review and meta-analysis aimed to evaluate the long-term impact of metformin use in pregnancy on children and their mothers.
METHODS
Electronic databases were searched for studies evaluating metformin as compared to insulin for managing GDM/DIP. Primary outcome was to evaluate changes in body-mass index (BMI) in children at 5-11 years age. Secondary outcomes were to assess alterations in other anthropometric measures, obesity, changes in lipids and adipo-cytokines in children and mothers.
RESULTS
Children at 9-years age, born to mothers who were treated with metformin during pregnancy had similar BMI [MD1.09kg/m(95%CI:-0.44-2.62);P=0.16;I=16%], waist-circumference to height-ratio [MD0.13(95%CI:-0.05-0.30);P=0.16;I=94%], dual-energy X-ray absorptiometry (DXA) total fat-mass [MD0.68kg(95%CI:-2.39-3.79);P=0.66;I=70%], DXA-total fat-percent [MD 0.04%(95%CI:-3.44-3.51);P=0.98;I=56%], DXA-total fat-free mass [MD 0.81kg (95%CI:-0.96-2.58);P=0.37;I=55%], MRI visceral adipose tissue [MD 80.97cm(95%CI:-136.47-298.41); P=0.47;I=78%] and magnetic-resonance spectroscopy liver-fat percentage [MD 0.27%(95% CI:-1.26-1.79);P=0.73;I=0%], compared to those born to mothers who were treated with insulin. Serum adiponectin, leptin, alanine-aminotransferase and ferritin were comparable among groups. In children between 9-11 years age, occurrence of obesity, diabetes or challenges in motor and social development were comparable between the 2 groups. After 9 years of childbirth, BMI and risk of developing diabetes were similar in the two groups of women.
CONCLUSION
Metformin use in pregnancy did not show any adverse effects when compared to insulin on long-term outcomes in children and their mothers.
PubMed: 38876183
DOI: 10.1016/j.eprac.2024.05.017 -
Annales D'endocrinologie Jun 2024During the past years, several drugs have been developed for the treatment of obesity. Some are already used in clinical practice: orlistat, GLP-1 receptor agonists... (Review)
Review
During the past years, several drugs have been developed for the treatment of obesity. Some are already used in clinical practice: orlistat, GLP-1 receptor agonists (RA), GLP-1/GIP biagonists and the melanocortin 4 receptor (MC4R) agonist, setmelanotide. Some should be available in the future: GLP-1/glucagon biagonists, GLP-1/GIP/glucagon triagonists. These drugs act mainly by reducing food intake or fat absorption. However, many of them show specific effects on the adipose tissue. All these drugs show significant reduction of fat mass and, more particularly of visceral fat. If most of the drugs, except orlistat, have been shown to increase energy expenditure in rodents with enhanced thermogenesis, this has not yet been clearly demonstrated in humans. However, biagonists or triagonist stimulating glucagon seem to a have a more potent effect to increase thermogenesis in the adipose tissue and, thus, energy expenditure. Most of these drugs have been shown to increase the production of adiponectin and to reduce the production of pro-inflammatory cytokines by the adipose tissue. GLP-1RAs reduce the size of adipocytes and promote their differentiation. GLP-1RAS and GLP-1/GIP biagonists reduce, in the adipose tissue, the expression of several genes involved in lipogenesis. Further studies are still needed to clarify the precise roles, on the adipose tissue, of these drugs dedicated for the treatment of obesity.
Topics: Humans; Obesity; Anti-Obesity Agents; Adipose Tissue; Animals; Energy Metabolism; Glucagon-Like Peptide-1 Receptor; Thermogenesis; Glucagon-Like Peptide 1; Orlistat
PubMed: 38871515
DOI: 10.1016/j.ando.2024.05.021 -
BMC Genomics Jun 2024Intramuscular fat content is an important index reflecting the quality of mutton, which directly affects the flavor and tenderness of mutton. Livestock and poultry...
BACKGROUND
Intramuscular fat content is an important index reflecting the quality of mutton, which directly affects the flavor and tenderness of mutton. Livestock and poultry intramuscular fat content is influenced by genetics, nutritional level, and environmental factors. Key regulatory factors play a crucial role in intramuscular fat deposition. However, there is a limited amount of research on the identification and function of key genes involved in intramuscular fat content deposition specifically in sheep.
RESULTS
Histological differences in the longest dorsal muscle of the small-tailed frigid sheep increased in diameter and decreased in several muscle fibers with increasing monthly age; The intramuscular fat content of the longest dorsal muscle of the small-tailed cold sheep varied with age, with a minimum of 1 month of age, a maximum of 6 months of age, and a minimum of 12 months of age. Transcriptomic sequencing and bioinformatics analysis revealed a large number of differential genes in the longest dorsal muscles of little-tailed billy goats of different months of age, which were enriched in multiple GO entries and KEGG pathways. Among them, the pathway associated with intramuscular fat was the AMPK signaling pathway, and the related genes were PPARGC1A and ADIPOQ; Immunohistochemical studies showed that PPARGC1A and ADIPOQ proteins were expressed in connective tissues, cell membranes, and, to a lesser extent, the cytoplasm of the longest dorsal muscle of the little-tailed frigid sheep; Real-time PCR and Western Blot validation showed that PPARGC1A and ADIPOQ were both expressed in the longest dorsal muscle of the little-tailed frigid sheep at different ages, and there were age differences in the amount of expression. The ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle, and the PPARGC1A gene was positively correlated with the intramuscular fat content of the longest dorsal muscle; As inferred from the above results, the ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle (r = -0.793, P < 0.05); and the PPARGC1A gene was positively correlated with the intramuscular fat content of the longest dorsal muscle r = 0.923, P < 0.05).
CONCLUSIONS
Based on the above results, it can be inferred that the ADIPOQ gene is negatively correlated with the intramuscular fat content of the longest back muscle (r = -0.793, P < 0.05); the PPARGC1A gene is positively correlated with the intramuscular fat content of the longest back muscle (r = 0.923, P < 0.05).
Topics: Animals; Sheep; Muscle, Skeletal; Adipose Tissue; Adiponectin; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Gene Expression Profiling; Transcriptome
PubMed: 38867146
DOI: 10.1186/s12864-024-10486-w -
Scientific Reports Jun 2024Aging enhances numerous processes that compromise homeostasis and pathophysiological processes. Among these, activated HSCs play a pivotal role in advancing liver...
Aging enhances numerous processes that compromise homeostasis and pathophysiological processes. Among these, activated HSCs play a pivotal role in advancing liver fibrosis. This research delved into how aging impacts liver fibrosis mechanisms. The study involved 32 albino rats categorized into four groups: Group I (young controls), Group II (young with liver fibrosis), Group III (old controls), and Group IV (old with liver fibrosis). Various parameters including serum ALT, adiponectin, leptin, and cholesterol levels were evaluated. Histopathological analysis was performed, alongside assessments of TGF-β, FOXP3, and CD133 gene expressions. Markers of fibrosis and apoptosis were the highest in group IV. Adiponectin levels significantly decreased in Group IV compared to all other groups except Group II, while cholesterol levels were significantly higher in liver fibrosis groups than their respective control groups. Group III displayed high hepatic expression of desmin, α-SMA, GFAP and TGF- β and in contrast to Group I. Increased TGF-β and FOXP3 gene expressions were observed in Group IV relative to Group II, while CD133 gene expression decreased in Group IV compared to Group II. In conclusion, aging modulates immune responses, impairs regenerative capacities via HSC activation, and influences adipokine and cholesterol levels, elevating the susceptibility to liver fibrosis.
Topics: Animals; Hepatic Stellate Cells; Liver Cirrhosis; Rats; Aging; Male; Transforming Growth Factor beta; Cholesterol; Apoptosis; Liver
PubMed: 38866800
DOI: 10.1038/s41598-024-63644-1 -
Lifestyle Genomics Jun 2024The effects of the rs822393 variant of ADIPOQ gene on metabolic parameters such as insulin resistance and adiponectin levels following weight loss through dietary...
INTRODUCTION
The effects of the rs822393 variant of ADIPOQ gene on metabolic parameters such as insulin resistance and adiponectin levels following weight loss through dietary intervention are still uncertain. The aim of this study was to evaluate the role of rs822393 of ADIPOQ gene on adiponectin levels and metabolic parameters after weight loss with a high fat hypocaloric diet with Mediterranean pattern during 12 weeks.
METHODS
A population of 283 patients with obesity were allocated to a dietary intervention trial with a high fat hypocaloric diet during 12 weeks. Adiposity and biochemical parameters were determined. rs822393 was assessed with a dominant model analysis (CC vs CT+TT). Results These patients had three different genotypes: CC (59.0%), CT (33.6%), and TT (7.4%). The allelic frequencies for C and T were 0.89 and 0.20, respectively. Basal and post-intervention HDL cholesterol, adiponectin levels and adiponectin/leptin ratio were lower in T-allele than non-T-allele carriers. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin, HOMA-IR, leptin, total cholesterol and LDL-cholesterol levels improved significantly in both genotype groups. Moreover, HDL-cholesterol (CC vs CT+TT) (delta:8.9+1.1 mg/dl vs. 1.7+0.8 mg/dl; p=0.02), serum adiponectin in non-T allele carriers (43.1 ± 5.9 ng/dl vs. 2.8 ±3 .0 ng/dl; p=0.01) and adiponectin/leptin ratio (1.37± 0.1 units vs. 0.17± 0.08 units; p=0.02) improved only in non-T allele carriers after weight loss.
CONCLUSION
Individuals with obesity and without the T allele of rs822393 experienced improvements in adiponectin levels, adiponectin/leptin ratio and HDL-cholesterol levels after following a high-fat hypocaloric diet with a Mediterranean pattern.
PubMed: 38865975
DOI: 10.1159/000539056 -
Calcified Tissue International Jun 2024Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to...
Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.
PubMed: 38864922
DOI: 10.1007/s00223-024-01240-1