Accumulating evidence demonstrates that adipose tissue is a major site of tumor necrosis factor-alpha (TNF-alpha) gene expression, which is markedly high in obese animals and may contribute to obesity-linked insulin resistance. We now report that recombinant murine TNF-alpha triggers the apoptotic degeneration of brown adipocytes differentiated in culture. Moreover, noradrenaline, which has been described as having trophic effects on brown fat and accelerating the differentiation of brown adipocytes, is capable of dose-dependently preventing the TNF-alpha-induced apoptosis of brown fat cells. Since obesity is characterized by greatly increased TNF-alpha production and reduced catecholaminergic activity, apoptosis was studied in the brown fat of genetically obese animals. In situ DNA fragmentation analysis revealed a larger number of apoptotic cells in the brown fat of obese (fa/fa) than in that of lean (+/+) Zucker rats. The exposure of obese rats to low temperatures for 7 days, which increases the sympathetic activity of brown adipose tissue, significantly reduces the number of apoptotic brown adipocytes. We hypothesize that TNF-alpha may play a significant role in the control of brown fat homeostasis.
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http://dx.doi.org/10.1038/sj.cdd.4400292 | DOI Listing |
Clin Nutr
December 2024
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Nutrition, University of California Davis, Davis, CA, USA; Department of Radiology, University of California Davis, Sacramento, CA, USA; Department of Nutritional Sciences and Dietetics, Harokopio University of Athens, Greece. Electronic address:
Background & Aims: Brown adipose tissue (BAT) has been mainly investigated as a potential target against cardiometabolic disease, but it has also been linked to cancer-related outcomes. Although preclinical data support that BAT and the thermogenic adipocytes in white adipose tissue may play an adverse role in the pathogenesis of cancer cachexia, results from studies in patients have reported inconsistent results. The purpose of this study was to examine the interrelationship between presence of detectable BAT, changes in body weight, and cachexia in patients with cancer.
View Article and Find Full Text PDFAging (Albany NY)
January 2025
Department of Pathology, Yale University School of Medicine, New Haven, CT 06519, USA.
Studies of the aging transcriptome focus on genes that change with age. But what can we learn from age-invariant genes-those that remain unchanged throughout the aging process? These genes also have a practical application: they can serve as reference genes in expression studies. Reference genes have mostly been identified and validated in young organisms, and no systematic investigation has been done across the lifespan.
View Article and Find Full Text PDFClin Sci (Lond)
January 2025
Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA.
Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.
View Article and Find Full Text PDFFront Drug Deliv
December 2024
VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA 98108, USA.
Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (T) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats.
View Article and Find Full Text PDFVitam Horm
January 2025
Lilly Diabetes Research Center, Indiana Biosciences Research Institute, Indianapolis, IN, United States; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United States. Electronic address:
The hypothalamus plays a central role in regulating energy expenditure and maintaining energy homeostasis, crucial for an organism's survival. Located in the ventral diencephalon, it is a dynamic and adaptable brain region capable of rapid responses to environmental changes, exhibiting high anatomical and cellular plasticity and integrates a myriad of sensory information, internal physiological cues, and humoral factors to accurately interpret the nutritional state and adjust food intake, thermogenesis, and energy homeostasis. Key hypothalamic nuclei contain distinct neuron populations that respond to hormonal, nutrient, and neural inputs and communicate extensively with peripheral organs like the gastrointestinal tract, liver, pancreas, and adipose tissues to regulate energy production, storage, mobilization, and utilization.
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