Cpt1a silencing in AgRP neurons improves cognitive and physical capacity and promotes healthy aging in male mice.

Orexigenic neurons expressing agouti-related protein (AgRP) and neuropeptide Y in the arcuate nucleus (ARC) of the hypothalamus are activated in response to dynamic variations in the metabolic state, including exercise. We previously observed that carnitine palmitoyltransferase 1a (CPT1A), a rate-limiting enzyme of mitochondrial fatty acid oxidation, is a key factor in AgRP neurons, modulating whole-body energy balance and fluid homeostasis. However, the effect of CPT1A in AgRP neurons in aged mice and during exercise has not been explored yet. We have evaluated the physical and cognitive capacity of adult and aged mutant male mice lacking Cpt1a in AgRP neurons (Cpt1a KO). Adult Cpt1a KO male mice exhibited enhanced endurance performance, motor coordination, locomotion, and exploration compared with control mice. No changes were observed in anxiety-related behavior, cognition, and muscle strength. Adult Cpt1a KO mice showed a reduction in gastrocnemius and tibialis anterior muscle mass. The cross-sectional area (CSA) of these muscles were smaller than those of control mice displaying a myofiber remodeling from type II to type I fibers. In aged mice, changes in myofiber remodeling were maintained in Cpt1a KO mice, avoiding loss of physical capacity during aging progression. Additionally, aged Cpt1a KO mice revealed better cognitive skills, reduced inflammation, and oxidative stress in the hypothalamus and hippocampus. In conclusion, CPT1A in AgRP neurons appears to modulate health and protects against aging. Future studies are required to clarify whether CPT1A is a potential antiaging candidate for treating diseases affecting memory and physical activity.

Purging behavior modulates the relationships of hormonal and behavioral parameters in women with eating disorders.

BACKGROUND/AIMS: There is ample consensus that there is a neurophysiological basis for eating disorders (ED). Traits of personality translate into behavioral traits, purging being a well-defined transversal example. The direct implication of steroid hormones on ED has seldom been studied, despite their effects on behavior. METHODS: After psychological interview analysis, 57 ED female patients (31 purgative and 26 nonpurgative) and 17 female controls were studied. Metabolic parameters and analysis of androgen, estrogen and glucocorticoid hormones were determined in parallel to the psychopathological profile (EDI-2 and SCL-90-R) and anthropometric measurements. RESULTS: Psychometric tests showed clear differences between ED and controls, but there were few hormonal-metabolic significant differences. In purgative ED there were repeated (significant) positive correlations with corticosteroid-binding globulin (CBG) and negative correlations with sex hormone-binding globulin (SHBG) versus eating and general psychopathology. In nonpurging ED there were positive correlations for deoxycortisol, free fatty acids and albumin and negative for aspartate aminotransferase and psychopathological traits. CONCLUSION: The data suggest that CBG/corticosteroids and sexual hormones/SHBG are involved in purging behavior and its psychopathology and severity scores. Correlations of selected psychometric data and the CBG/SHBG levels in purging may eventually result in clinical markers. This approach may provide additional clues for understanding the pathogenesis of ED.

Site-related white adipose tissue lipid-handling response to oleoyl-estrone treatment in overweight male rats.

BACKGROUND: Oleoyl-estrone (OE) decreases energy intake while maintaining glucose homeostasis, and energy expenditure at the expense of body fat. White adipose tissue (WAT) depots behave differently under starvation, postprandial state and pharmacologically induced lipolysis. AIM OF THE STUDY: To understand the mechanism of massive lipid loss from WAT elicited by OE treatment. METHODS: We used overweight male rats. Rats receiving OE (10 nmol/g) gavages were compared with controls and a pair-fed group. Whole fat pads from the mesenteric, retroperitoneal, epididymal and inguinal subcutaneous sites were excised and analyzed for lipid, DNA, mRNA and the expression of lipogenic, fatty acid transporters and lipase genes. RESULTS: In OE and pair-fed rats, WAT weights decreased, with the limited loss of cells. Patterns of gene expression in most WAT sites were similar for OE and PF, suggesting a shared mechanism of fat mobilization, but in mesenteric WAT, PF increased lipogenic and fatty acid transporter gene expressions. However, OE inhibited lipogenic expressions more deeply than PF. CONCLUSIONS: White adipose tissue sites showed different expression patterns, hinting at relatively specialized functions in fat storage; thus, single site analyses cannot be extrapolated to whole WAT. Differences between mesenteric and the other sites suggest that 'visceral fat' should be reserved for this site only, and not applied to other abdominal fat depots (epididymal, retroperitoneal).

Gene expression modulation of liver energy metabolism by oleoyl-oestrone in overweight rats.

We intended to determine how the liver copes with the massive handling of lipids induced by OE (oleoyl-oestrone), as well as to characterize and differentiate the actual OE effects from those that may be only the consequence of decreased food intake. Thus we used male rats treated with oral OE (10 nmol/g per day) compared with a vehicle only PF (pair-fed) group and controls fed ad libitum (vehicle only). Plasma parameters, and total liver lipids, glycogen, DNA and total mRNA were measured. RNA was extracted and used for real-time PCR analysis of the gene expression of enzymes and regulatory factors of liver energy metabolism. Most hepatic proteins showed similar gene expressions in OE and controls, but the differences widened between OE and PF rats, showing that OE effects could not be merely attributed to a lower energy intake. The liver of OE-treated rats largely maintained its ability to mobilize glucose for the synthesis of fats; this was achieved in part by a peculiar combination of regulative modifications that facilitate both fatty acid disposal and restrained glucose utilization under conditions of limited food supply but ample availability of internal energy stores. In conclusion, the results presented suggest that the effect of OE on liver metabolism may be (at least in part) mediated through an insulin-sensitivity-dependent modulation of the expression of SREBP-1c (sterol-regulatory-element-binding protein-1c), resulting in the unique combined effect of mildly increased (or maintained) glucose disposal but also limited enhancement of lipogenesis.