Growth differentiation factor 15 (GDF15) and semaglutide inhibit food intake and body weight through largely distinct, additive mechanisms.

AIMS: To evaluate whether the potent hypophagic and weight-suppressive effects of growth differentiation factor-15 (GDF15) and semaglutide combined would be a more efficacious antiobesity treatment than either treatment alone by examining whether the neural and behavioural mechanisms contributing to their anorectic effects were common or disparate. MATERIALS/METHODS: Three mechanisms were investigated to determine how GDF15 and semaglutide induce anorexia: the potentiation of the intake suppression by gastrointestinal satiation signals; the reduction in motivation to feed; and the induction of visceral malaise. We then compared the effects of short-term, combined GDF15 and semaglutide treatment on weight loss to the individual treatments. Rat pharmaco-behavioural experiments assessed whether GDF15 or semaglutide added to the satiating effects of orally gavaged food and exogenous cholecystokinin (CCK). A progressive ratio operant paradigm was used to examine whether GDF15 or semaglutide reduced feeding motivation. Pica behaviour (ie, kaolin intake) and conditioned affective food aversion testing were used to evaluate visceral malaise. Additionally, fibre photometry studies were conducted in agouti-related protein (AgRP)-Cre mice to examine whether GDF15 or semaglutide, alone or in combination with CCK, modulate calcium signalling in hypothalamic AgRP neurons. RESULTS: Semaglutide reduced food intake by amplifying the feeding-inhibitory effect of CCK or ingested food, inhibited the activity of AgRP neurons when combined with CCK, reduced feeding motivation and induced malaise. GDF15 induced visceral malaise but, strikingly, did not affect feeding motivation, the satiating effect of ingested food or CCK signal processing. Combined GDF15 and semaglutide treatment produced greater food intake and body weight suppression than did either treatment alone, without enhancing malaise. CONCLUSIONS: GDF15 and semaglutide reduce food intake and body weight through largely distinct processes that produce greater weight loss and feeding suppression when combined.

MMPI-2 interpretation and closed-head trauma: cross-validation of a correction factor.

A substantial body of research suggests that the MMPI-2 contains a number of items that are sensitive to closed-head trauma (CHT) and other neurologic conditions. A correction procedure was recommended by Gass (1991) using an index consisting of 14 neurologically sensitive items that were extracted from a predominantly male veteran sample of CHT patients. The generalizability of these correction items was assessed in the present study by investigating the MMPI-2 scoring characteristics of an outpatient referral sample of 54 CHT patients (28 male, 26 female) who had sustained recent and mild head trauma. Their frequency of endorsement of MMPI-2 was contrasted with that of the MMPI-2 normative sample (N = 2,600). Chi-square analyses identified the 15 MMPI-2 items that best differentiated this CHT sample from normal subjects. The results indicate that: (a) unlike those in an inpatient psychiatric sample (n = 524), the MMPI-2 items that best distinguished the CHT Ss from normals consisted of neurologic symptom content; (b) of these 15 items, 10 were included in the 14-item correction (Gass, 1991); and (c) 13 of the 14 correction items effectively discriminated the cross-validation sample of CHT Ss from normals. These findings offer empirical support for the application of the MMPI-2 correction with patients who have mild and recent head trauma.

Visuoconstructive deficit following infarction in the right basal ganglia: a case report and some experimental data.

Visuospatial disorders are typically described as a consequence of right hemisphere, cortical lesions. We report the case of a female with visuoconstructive deficits with an infarct in the right basal ganglia, with no evidence of visual field defect, hemi-inattention, or sensory or motor loss. Using a process approach to obtain additional quantitative data, we showed that her visuoconstructive disorder could not be attributed to a defect in visual perception, per se. All other aspects of her neuropsychologic skills were normal. These findings provide additional support for the role of subcortical structures in spatially-related motor function and for the utility of applying experimental techniques to clarify the nature of deficits.