Peripherally administered baclofen reduced food intake and body weight in db/db as well as diet-induced obese mice.
(57/644)
Peripheral administration of baclofen significantly reduced food intake and body weight increase in both diabetic (db/db) and diet-induced obese mice for 5 weeks, whereas it had no significant effects on energy balance in their lean control mice. Despite the decreased body weight, neuropeptide Y expression in the arcuate nucleus was significantly decreased, whereas pro-opiomelanocortin expression was significantly increased by baclofen treatment. These data demonstrate that the inhibitory effects of baclofen on body weight in the obese mice were mediated via the arcuate nucleus at least partially, and suggest that GABA(B) agonists could be a new therapeutic reagent for obesity. (+info)
Developmental origin of fat: tracking obesity to its source.
(58/644)
The development of obesity not only depends on the balance between food intake and caloric utilization but also on the balance between white adipose tissue, which is the primary site of energy storage, and brown adipose tissue, which is specialized for energy expenditure. In addition, some sites of white fat storage in the body are more closely linked than others to the metabolic complications of obesity, such as diabetes. In this Review, we consider how the developmental origins of fat contribute to its physiological, cellular, and molecular heterogeneity and explore how these factors may play a role in the growing epidemic of obesity. (+info)
Cooperation between BAT and WAT of rats in thermogenesis in response to cold, and the mechanism of glycogen accumulation in BAT during reacclimation.
(59/644)
Rats were exposed to cold and then reacclimated at neutral temperature. Changes related to fatty acid and glucose metabolism in brown and white adipose tissues (BAT and WAT) and in muscle were then examined. Of the many proteins involved in the metabolic response, two lipogenic enzymes, acetyl-coenzyme A carboxylase (ACC) and ATP-citrate lyase, were found to play a pervasive role and studied in detail. Expression of the total and phosphorylated forms of both lipogenic enzymes in response to cold increased in BAT but decreased in WAT. Importantly, in BAT, only the phosphorylation of the ACC1 isoenzyme was enhanced, whereas that of ACC2 remained unchanged. The activities of these enzymes and the in vivo rate of FFA synthesis together suggested that WAT supplies BAT with FFA and glucose by decreasing its own synthetic activity. Furthermore, cold increased the glucose uptake of BAT by stimulating the expression of components of the insulin signaling cascade, as observed by the enhanced expression and phosphorylation of Akt and GSK-3. In muscle, these changes were observed only during reacclimation, when serum insulin also increased. Such changes may be responsible for the extreme glycogen accumulation in the BAT of rats reacclimated from cold. (+info)
Adipose tissue as an endocrine organ: from theory to practice.
(60/644)
OBJECTIVE: To describe the advances in research into the physiological role of white adipose tissue, with emphasis on its endocrinal role in inflammatory processes, feeding behavior, insulin sensitization and modulation of the atherogenetic process. To deal with the potential role of adipose tissue as a source of stem cells for regeneration of tissues, with special emphasis on adipogenesis and its consequences for development of obesity. SOURCES: Important information was compiled from the scientific literature in order that this analysis contains an explanatory synthesis of the aspects mentioned above. SUMMARY OF THE FINDINGS In addition to its classical functions as primary metabolic energy store, meeting energy requirements during periods of deprivation by means of lypolisis, adipose tissue also has the capacity to synthesize and secrete a variety of hormones - the adipokines. These are active in a range of processes, such as control of nutritional intake (leptin) and control of sensitivity to insulin and inflammatory processes (TNF-alpha, IL-6, resistin, visfatin, adiponectin). Furthermore, since adipose tissue also contains undifferentiated cells, it has the ability to generate new adipocytes, regenerating its own tissue (adipogenesis), and also the ability to give rise to other cells (myoblasts, chondroblasts, osteoblasts), which has great therapeutic potential in the not-too-distant future. CONCLUSIONS: The range of functional possibilities of adipose tissue has widened. An understanding of these potentials could make this tissue a great ally in the fight against conditions that are currently assuming epidemic proportions (obesity, diabetes mellitus, arterial hypertension and arteriosclerosis) and in which adipose tissue is still seen as the enemy. (+info)
Fat pad-specific effects of lipectomy on foraging, food hoarding, and food intake.
(61/644)
Unlike most species, after food deprivation, Siberian hamsters increase foraging and food hoarding, two appetitive ingestive behaviors, but not food intake, a consummatory ingestive behavior. We previously demonstrated (Wood AD, Bartness TJ, Am J Physiol Regul Integr Comp Physiol 272: R783-R792, 1997) that increases in food hoarding are triggered by directly decreasing body fat levels through partial surgical lipectomy; however, we did not test if lipectomy affected foraging, nor if the magnitude of the lipid deficit affected food hoard size. Therefore, we tested whether varying the size of the lipectomy-induced lipid deficit and/or foraging effort affected foraging, food hoarding, or food intake. This was accomplished by housing adult male Siberian hamsters in a foraging/hoarding system and removing (x) both epididymal white adipose tissue (EWATx) pads, both inguinal white adipose tissue (IWATx) pads, or both EWAT and IWAT pads (EWATx + IWATx) and measuring foraging, food hoarding, and food intake for 12 wk. The lipectomy-induced lipid deficit triggered different patterns of white adipose tissue mass compensation that varied with foraging effort. Foraging for food (10 wheel revolutions to earn a food pellet) abolished the EWATx-induced compensation in IWAT pad mass. The magnitude of the lipid deficit did not engender a proportional change in any of the appetitive or consummatory ingestive behaviors. EWATx caused the greatest increase in food hoarding compared with IWATx or EWATx + IWATx, when animals were required to forage for their food. Collectively, it appears that the magnitude of a lipid deficit does not affect appetitive or consummatory behaviors; rather, when energy (foraging) demands are increased, loss of specific (gonadal) fat pads can preferentially stimulate increases in food hoarding. (+info)
Localized proton magnetic resonance spectroscopy of lipids in adipose tissue at high spatial resolution in mice in vivo.
(62/644)
We describe a localized proton magnetic resonance spectroscopy ((1)H-MRS) method for in vivo measurement of lipid composition in very small voxels (1.5 mm x 1.5 mm x 1.5 mm) in adipose tissue in mice. The method uses localized point-resolved spectroscopy to collect (1)H spectra from voxels in intra-abdominal white adipose tissue (WAT) and brown adipose tissue (BAT) deposits. Nonlinear least-squares fits of the spectra in the frequency domain allow for accurate calculation of the relative amount of saturated, monounsaturated, and polyunsaturated fatty acids. All spectral data are corrected for spin-spin relaxation. The data show BAT of NMRI mice to be significantly different from BAT of NMRI nu/nu mice in all aspects except for the fraction of monounsaturated fatty acids (FM); for WAT, only the FM is different. BAT and WAT of NMRI mice differ in the amount of saturated and di-unsaturated fatty acids. This method provides a potential tool for studying lipid metabolism in small animal models of disease during the initiation, progression, and manifestation of obesity-related disorders in vivo. Our results clearly demonstrate that localized (1)H-MRS of adipose tissue in vivo is possible at high spatial resolution with voxel sizes down to 3.4 ml. (+info)
Dietary fish oil upregulates intestinal lipid metabolism and reduces body weight gain in C57BL/6J mice.
(63/644)
Fish oils (FO) rich in (n-3) PUFA exert hypolipidemic and antiobesity effects in association with modulated hepatic lipid metabolism. We recently demonstrated the possible involvement of intestinal lipid metabolism in the development of obesity. In this study, we examined the effect of FO ingestion on intestinal lipid metabolism in relation to obesity. When diet-induced obesity-prone C57BL/6J mice were fed an 8% FO, high-fat (30%) diet for 5 mo, body weight gain was significantly reduced compared with mice fed a 30% triacylglycerol (TG) diet without FO. In addition to modulating messenger RNA (mRNA) levels in the liver, FO ingestion for 2 wk affected the intestinal mRNA levels of lipid metabolism-related genes; those of carnitine palmitoyltransferase 1a, cytochrome P450 4A10, and malic enzyme were significantly higher in mice fed the 8% FO diet compared with mice fed the 30% TG diet. Northern blot analysis revealed that the expression levels of most lipid metabolism-related genes in the small intestine of mice fed the 8% FO diet were comparable to those in the liver. Furthermore, reflecting the difference at the mRNA level, FO ingestion affected lipid metabolism-related enzyme activity; fatty acid beta-oxidation, omega-oxidation, and malic enzyme activities in the small intestine of mice fed the 8% FO diet were 1.2-, 1.6-, and 1.7-fold those in mice fed the 30% TG diet, respectively. These findings suggest that an upregulation of intestinal lipid metabolism is associated with the antiobesity effect of FO. (+info)
Enhanced leptin-stimulated Pi3k activation in the CNS promotes white adipose tissue transdifferentiation.
(64/644)
The contribution of different leptin-induced signaling pathways in control of energy homeostasis is only partly understood. Here we show that selective Pten ablation in leptin-sensitive neurons (Pten(DeltaObRb)) results in enhanced Pi3k activation in these cells and reduces adiposity by increasing energy expenditure. White adipose tissue (WAT) of Pten(DeltaObRb) mice shows characteristics of brown adipose tissue (BAT), reflected by increased mitochondrial content and Ucp1 expression resulting from enhanced leptin-stimulated sympathetic nerve activity (SNA) in WAT. In contrast, leptin-deficient ob/ob-Pten(DeltaObRb) mice exhibit unaltered body weight and WAT morphology compared to ob/ob mice, pointing to a pivotal role of endogenous leptin in control of WAT transdifferentiation. Leanness of Pten(DeltaObRb) mice is accompanied by enhanced sensitivity to insulin in skeletal muscle. These data provide direct genetic evidence that leptin-stimulated Pi3k signaling in the CNS regulates energy expenditure via activation of SNA to perigonadal WAT leading to BAT-like differentiation of WAT. (+info)