Clinical interest in de novo lipogenesis has been sparked by recent studies in rodents demonstrating that de novo lipogenesis specifically in white adipose tissue produces the insulin-sensitizing fatty acid palmitoleate. By contrast, hepatic lipogenesis is thought to contribute to metabolic disease. How de novo lipogenesis in white adipose tissue versus liver is altered in human obesity and insulin resistance is poorly understood. Here we show that lipogenic enzymes and the glucose transporter-4 are markedly decreased in white adipose tissue of insulin-resistant obese individuals compared with non-obese controls. By contrast, lipogenic enzymes are substantially upregulated in the liver of obese subjects. Bariatric weight loss restored de novo lipogenesis and glucose transporter-4 gene expression in white adipose tissue. Notably, lipogenic gene expression in both white adipose tissue and liver was strongly linked to the expression of carbohydrate-responsive element-binding protein-β and to metabolic risk markers. Thus, de novo lipogenesis predicts metabolic health in humans in a tissue-specific manner and is likely regulated by glucose-dependent carbohydrate-responsive element-binding protein activation.
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http://dx.doi.org/10.1038/ncomms2537 | DOI Listing |
Molecules
January 2025
Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine of Porto, University of Porto, 4200-319 Porto, Portugal.
The prevalence of metabolic syndrome has been exponentially increasing in recent decades. Thus, there is an increasing need for affordable and natural interventions for this disorder. We explored the effect of chrysin, a dietary polyphenol, on hepatic lipid and glycogen accumulation, metabolic dysfunction-associated fatty liver disease (MAFLD) activity score and oxidative stress and on hepatic and adipose tissue metabolism in rats presenting metabolic syndrome-associated conditions.
View Article and Find Full Text PDFMicroorganisms
January 2025
Institute of Animal Husbandry, Jiangsu Academy of Agricultural Sciences, Nanjing 210094, China.
Emerging evidence indicates a close relationship between gut microbiota and fatty liver disease. It has been suggested that gut microbiota modulation with probiotics ameliorates fatty liver disease in rodents and humans, yet it remains unclear whether the same results will also be obtained in poultry. The aim of this study was to investigate whether a mixture of probiotics supplemented after hatching can prevent CORT-induced fatty liver disease in broilers, and to determine how such effects, if any, are associated with hepatic de novo lipogenesis and gut microbiota composition.
View Article and Find Full Text PDFLiver Int
February 2025
Department of Digestive and Hepatobiliary Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France.
Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of hepatocellular carcinoma (HCC). In this study, we combine metabolomic and gene expression analysis to compare HCC tissues with non-tumoural tissues (NTT).
Methods: A non-targeted metabolomic strategy LC-MS was applied to 52 pairs of human MASLD-HCC and NTT separated into 2 groups according to fibrosis severity F0F1-F2 versus F3F4.
Endocrinology
January 2025
Department of Pediatrics, Divisions of Neonatology & Developmental Biology and Endocrinology, Neonatal Research Center of the UCLA Children's Discovery & Innovation Institute at the David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1752.
To determine the basis for perinatal nutritional mismatch causing metabolic dysfunction associated steatotic liver disease (MASLD) and diabetes mellitus, we examined adult phenotype, hepatic transcriptome, and pancreatic β-islet function. In prenatal caloric restricted rat with intrauterine growth restriction (IUGR) and postnatal exposure to high fat with fructose (HFhf) or high carbohydrate (RC), we investigated male and female IUGR-Hfhf and IUGR-RC, versus HFhf and CON offspring. Males more than females displayed adiposity, glucose intolerance, insulin resistance, hyperlipidemia, hepatomegaly with hepatic steatosis.
View Article and Find Full Text PDFJ Gastroenterol Hepatol
January 2025
Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India.
Background: Resmetirom, the first FDA-approved drug for nonalcoholic steatohepatitis (NASH) with fibrosis in obese patients, when combined with lifestyle modifications, improves NASH resolution and reduces fibrosis by at least one stage. Low thyroid hormone (T) levels are linked to a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). Epidemiological studies have confirmed the positive correlation between hypothyroidism and MASLD.
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