Data mining was performed on 28 330 unique peptide tandem mass spectra for which sequences were assigned with high confidence. By dividing the spectra into different sets based on structural features and charge states of the corresponding peptides, chemical interactions involved in promoting specific cleavage patterns in gas-phase peptides were characterized. Pairwise fragmentation maps describing cleavages at all Xxx-Zzz residue combinations for b and y ions reveal that the difference in basicity between Arg and Lys results in different dissociation patterns for singly charged Arg- and Lys-ending tryptic peptides. While one dominant protonation form (proton localized) exists for Arg-ending peptides, a heterogeneous population of different protonated forms or more facile interconversion of protonated forms (proton partially mobile) exists for Lys-ending peptides. Cleavage C-terminal to acidic residues dominates spectra from singly charged peptides that have a localized proton and cleavage N-terminal to Pro dominates those that have a mobile or partially mobile proton. When Pro is absent from peptides that have a mobile or partially mobile proton, cleavage at each peptide bond becomes much more prominent. Whether the above patterns can be found in b ions, y ions, or both depends on the location of the proton holder(s) in multiply protonated peptides. Enhanced cleavages C-terminal to branched aliphatic residues (Ile, Val, Leu) are observed in both b and y ions from peptides that have a mobile proton, as well as in y ions from peptides that have a partially mobile proton; enhanced cleavages N-terminal to these residues are observed in b ions from peptides that have a partially mobile proton. Statistical tools have been designed to visualize the fragmentation maps and measure the similarity between them. The pairwise cleavage patterns observed expand our knowledge of peptide gas-phase fragmentation behaviors and may be useful in algorithm development that employs improved models to predict fragment ion intensities.

Analysis of fragmentation patterns from 5654 unique doubly charged tryptic peptides is obtained. Great variability of average relative abundance of bond cleavage is found between different amino acid combinations. There exist similarities as well as differences between b and y ions. Strong enhancement or suppression of cleavage gives insight into possible chemical interactions at reactive conformations formed by preferred phi-psi angles.

Chronic diet-induced obesity developed in 50-60% of male Sprague-Dawley rats fed a relatively high-calorie diet for 90 days. The remaining rats decreased their caloric intake and resisted the development of obesity. All male Fischer F-344 rats fed this diet for 85 days became obese but to only half the degree of the obese Sprague-Dawley rats. The development of chronic obesity in both rat strains was associated with decreased norepinephrine (NE) levels in hearts and aortas and decreased NE turnover in aortas compared with chow-fed controls. However, 40-50% of the Sprague-Dawley rats did not become obese on this diet, yet showed similar findings suggesting an effect of dietary composition on sympathetic function. The more profoundly obese Sprague-Dawley rats additionally showed decreased or absent NE turnover in their hearts and pancreases. Since sympathetic function in both strains of rats with diet-induced obesity was either depressed or normal, it appears unlikely that the initial enhancement of sympathetic activity seen during short-term overfeeding plays an important continuing role in combating more chronic states of obesity in the rat.

The purpose of these investigations was to ascertain the effect of (−)‐hydroxycitrate on the accumulation of lipid in the meal fed rat by examining the rates of lipogenesis after acute and chronic treatment. Oral administration of (−)‐hydroxycitrate depressed significantly the in vivo lipogenic rates in a dose‐dependent manner in the liver, adipose tissue, and small intestine. The hepatic inhibition was significant for the 8 hr period, when control animals demonstrated elevated rates of lipid synthesis. The kinetics of this reduction of in vivo hepatic lipogenesis were identical after acute or chronic administration of (−)‐hydroxycitrate. However, in vitro rates of lipogenesis were elevated after chronic administration of (−)‐hydroxycitrate for 30 days. Rats receiving (−)‐hydroxycitrate consumed less food than the untreated controls; however, this decreased caloric intake was not responsible for the drug induced depression of hepatic lipogenesis, as shown by studies using pair fed rats.

Sprague-Dawley rats developed diet-induced obesity (DIO) after 3 mo on a high-fat, high-sucrose diet (DIO diet), with associated increases in total body and interscapular brown adipose tissue (IBAT) lipid content. After 7 days on the DIO diet, rats had increased levels of tyrosine hydroxylase (TH; 34%), norepinephrine (NE; 34%), and NE turnover (94%; estimated by alpha-methyl-p-tyrosine inhibition of TH) in their IBAT compared with chow-fed controls. After 3 mo on the DIO diet, NE levels and/or turnover were reduced by 27-50% in aortas, hearts, and pancreata in obese rats. While IBAT NE turnover was normal, TH inhibition failed to increase the lipid content of IBAT in obese rats as it did in controls, suggesting a postsynaptic defect in basal NE-stimulated lipolysis in this thermogenically active tissue. When obese rats were switched from the DIO diet to rat chow for 3 days, NE levels remained depressed in their hearts (25%) and aortas (14%) but were increased by 36-45% in IBAT, pancreata, and white adipose tissue. NE turnover rates and/or constants were increased by 37-110% in hearts, aortas, pancreata, and IBAT of these obese rats while there were increased IBAT TH (20%) and dopamine-beta-hydroxylase (87%) activities compared with chow-fed controls. Therefore, sympathetic activity varied markedly as a function of both dietary composition and relative body weight during the development of DIO.

After 15 wk on a moderately high-calorie high-fat (CM) diet, 43% of 40 3-mo-old male Sprague-Dawley rats developed diet-induced obesity (DIO) (29% more weight gain), whereas 57% of diet-resistant (DR) rats gained no more weight than 20 chow-fed controls. When switched to chow for another 7 wk, DR rats ate 13% less, gained 55% less weight, and had 49% lower food efficiency, whereas DIO rats ate 4% less but had comparable weight gain and efficiency to controls. DIO rats had 29% more carcass lipid (percent of carcass weight). DIO rat retroperitoneal white adipose pads had 65% more cells that were the same size as those in chow-fed pads; DR rat cells were similar to controls. Both DR and DIO rats increased norepinephrine turnover in their interscapular brown adipose pads by greater than 90%. DIO rats also had 40% lower pancreatic turnover; their plasma insulin levels were 327% of controls after 15 wk on the CM diet and 188% after 7 wk on chow. DR levels were the same as controls at both times. Therefore, regulation of caloric intake, pancreatic sympathetic tone, and plasma insulin levels were three important differences between rats that resisted and those that developed DIO on high-energy diets.

No abstract

No abstract