Day–night pattern of energy expenditure and body temperature in cachectic tumour-bearing rats

The implication of an increase in energy expenditure in cancer cachexia, which seems to be related to the type of tumour, remains unclear. We therefore investigated the energy metabolism and body temperature in anorectic and cachectic rats bearing the Yoshida sarcoma (TB), in comparison with pair-fed (PF) and ad-libitum fed (AL) control rats. The resting energy expenditure was higher in the TB than in the two control groups when corrected for the modifications of body composition. However, the total energy expenditure did not differ between the TB and the AL, presumably because of the drop of activity in TB. There was a temporal distribution of differences in energy expenditure with higher energy expenditure in TB than in AL during the diurnal phase and a lack of difference during the nocturnal phase. The TB presented a fever, which was limited to the diurnal period. Moreover, the acrophase of the body temperature rhythm was delayed in the TB. These results highlight the circadian effects of tumour development on the energy metabolism of the host and hint to the possible implication of cytokines. © 2000 Harcourt Publishers Ltd © 2000 Cancer Research Campaig

CD36 Inhibitors Reduce Postprandial Hypertriglyceridemia and Protect against Diabetic Dyslipidemia and Atherosclerosis

CD36 is recognized as a lipid and fatty acid receptor and plays an important role in the metabolic syndrome and associated cardiac events. The pleiotropic activity and the multiple molecular associations of this scavenger receptor with membrane associated molecules in different cells and tissues have however questioned its potential as a therapeutic target. The present study shows that it is possible to identify low molecular weight chemicals that can block the CD36 binding and uptake functions. These inhibitors were able to reduce arterial lipid deposition, fatty acid intestinal transit, plasma concentration of triglycerides and glucose, to improve insulin sensitivity, glucose tolerance and to reduce the plasma concentration of HbAc1 in different and independent rodent models. Correlation between the anti-CD36 activity of these inhibitors and the known pathophysiological activity of this scavenger receptor in the development of atherosclerosis and diabetes were observed at pharmacological doses. Thus, CD36 might represent an attractive therapeutic target

Necdin Controls Proliferation of White Adipocyte Progenitor Cells

White adipose tissues are composed mainly of white fat cells (adipocytes), which play a key role in energy storage and metabolism. White adipocytes are terminally differentiated postmitotic cells and arise from their progenitor cells (preadipocytes) or mesenchymal stem cells residing in white adipose tissues. Thus, white adipocyte number is most likely controlled by the rate of preadipocyte proliferation, which may contribute to the etiology of obesity. However, little is known about the molecular mechanisms that regulate preadipocyte proliferation during adipose tissue development. Necdin, which is expressed predominantly in postmitotic neurons, is a pleiotropic protein that possesses anti-mitotic and pro-survival activities. Here we show that necdin functions as an intrinsic regulator of white preadipocyte proliferation in developing adipose tissues. Necdin is expressed in early preadipocytes or mesenchymal stem cells residing in the stromal compartment of white adipose tissues in juvenile mice. Lentivirus-mediated knockdown of endogenous necdin expression in vivo in adipose tissues markedly increases fat mass in juvenile mice fed a high-fat diet until adulthood. Furthermore, necdin-null mutant mice exhibit a greater expansion of adipose tissues due to adipocyte hyperplasia than wild-type mice when fed the high-fat diet during the juvenile and adult periods. Adipose stromal-vascular cells prepared from necdin-null mice differentiate in vitro into a significantly larger number of adipocytes in response to adipogenic inducers than those from wild-type mice. These results suggest that necdin prevents excessive preadipocyte proliferation induced by adipogenic stimulation to control white adipocyte number during adipose tissue development

Reverse Physiology, i.e., Cellular Versus Integrative Versus Comparative Physiology? alpha-2 Agonists and Septic Shock

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Adipocytes as lipid sensors of oleic acid transport through a functional Caco-2/HT29-MTX intestinal barrier

Adipose tissue function in the regulation of lipemia is highly dependent on intestinal absorption of nutrients. Therefore the aim of the present study was the development and validation of an in vitro multiculture model allowing to measure intestinal absorption using adipocytes as lipid sensors. We previously described (1) novel methods to study oleic acid induction of adipogenesis and lipogenesis and (2) a functional reconstituted intestinal barrier using human cell lines Caco-2/HT29-MTX (9:1). In the present study we develop a co-culture model with either adipocytes or hepatocytes as sensors for intestinal lipid absorption. This model was validated using oleic acid (OA) pre-absorbed onto the intestinal barrier. Optimized experimental conditions were obtained with partially differentiated 3T3L1-MBX adipocytes sensing up to 5 muM OA in solution or 40 muM OA pre-absorbed by Caco2/HT29-MTX intestinal barriers. Metabolism including glycemia and insulinemia greatly influenced the ability to TG accumulation in adipocytes. By comparison AML12 hepatocytes found less sensitive to OA (up to 1 muM). The present study demonstrates a much better functionality for fatty acid uptake and release in Caco2/HT29-MTX versus Caco-2 intestinal barriers. Taken together these results open new opportunities to study in vitro lipid transfer between intestinal barriers and either adipocytes or hepatocytes. Abbreviations: BSA: Bovine serum albumin; CIDEs: Cell Death Inducing DFFA Like Effectors; DMEM, Dulbecco's Modified Eagle's Medium; FABPs: Fatty Acid Binding Proteins; FAT/CD36: Fatty acid translocase; FCS: Fetal calf serum; GLP2: Glucagon-like peptide-2; NAFLD: Nonalcoholic fatty liver disease; OA: oleic acid; PBS: Phosphate buffer saline; PPARs: Peroxisome-Proliferator Activated Receptors; RTCA: realtime cell analysis; TG: triglyceride

8 nm nanodiamonds as markers for 2 photon excited luminescent microscopy

International audienceStructural and luminescent properties of stable suspensions of fluorescent nanodiamonds were investigated. Measurement of the effective hydrodynamic radius yields particles less than 30 nm diameter, while the TEM measurements made on the same particles shows average diameter about 8 nm. It was found that NDs have relatively low toxicity. Upon incubation, 3T3-L1 cells spontaneously take up nanodiamonds that uniformly distribute in cells cytoplasm. The possibility of fluorescent imaging using both single ore two-photon excitation was shown