A horizontal view of primary metabolomes in vegetative desiccation tolerance.

Vegetative desiccation tolerance (VDT), the ability of such tissues to survive the near complete loss of cellular water, is a rare but polyphyletic phenotype. It is a complex multifactorial trait, typified by universal (core) factors but with many and varied adaptations due to plant architecture, biochemistry and biotic/abiotic dynamics of particular ecological niches. The ability to enter into a quiescent biophysically stable state is what ultimately determines desiccation tolerance. Thus, understanding the metabolomic complement of plants with VDT gives insight into the nature of survival as well as evolutionary aspects of VDT. In this study, we measured the soluble carbohydrate profiles and the polar, TMS-derivatisable metabolomes of 7 phylogenetically diverse species with VDT, in contrast with two desiccation sensitive (DS) species, under conditions of full hydration, severe water deficit stress, and desiccation. Our study confirmed the existence of core mechanisms of VDT systems associated with either constitutively abundant trehalose or the accumulation of raffinose family oligosaccharides and sucrose, with threshold ratios conditioned by other features of the metabolome. DS systems did not meet these ratios. Considerable chemical variations among VDT species suggest that co-occurring but distinct stresses (e.g., photooxidative stress) are dealt with using different chemical regimes. Furthermore, differences in the timing of metabolic shifts suggest there is not a single "desiccation programme" but that subprocesses are coordinated differently at different drying phases. There are likely to be constraints on the composition of a viable dry state and how different adaptive strategies interact with the biophysical constraints of VDT.

Environmental life cycle assessment of production of the high intensity sweetener steviol glycosides from Stevia rebaudiana leaf grown in Europe: The SWEET project.

Purpose: There is an increasing interest in the use of non-nutritive sweeteners to replace added sugar in food and beverage products for reasons of improving consumer health. Much work has been done to understand safety of sweeteners, but very little on sustainability. To address that gap, this study presents the results of a life cycle assessment (LCA) of production of rebaudioside A 60%, 95% pure (RA60) steviol glycoside mix from Stevia rebaudiana leaf grown in Europe. Methods: An attributional cradle-to-factory-gate life cycle assessment was conducted on growing of stevia leaves and extraction of steviol glycosides in Europe. Primary data were used from a case study supply chain. Results are reported in impact categories from the ReCiPe 2016 (H) method, with focus given to global warming potential, freshwater eutrophication, water consumption, and land use. Impacts are expressed both in terms of production mass and sweetness equivalence, a common metric for understanding high intensity sweetener potency. Sweetness equivalence of RA60 is typically 200 to 300 times that of sugar. Comparison of environmental impact is made to sugar (sucrose) produced from both cane and beets. The research is part of the EU project SWEET (sweeteners and sweetness enhancers: impact on health, obesity, safety, and sustainability). Results and discussion: Global warming potential for production of RA60 was found to be 20.25 kgCO2-eq/kgRA60 on a mass basis and 0.081 kgCO2-eq/kgSE on a sweetness equivalence basis. Field production of stevia leaves was found to be the main source of impact for most impact categories, and for all four focus categories. Extraction of the RA60 was the main source of impact for the others. Leaf processing and seedling propagation were minor contributors to life cycle impact. Removal of international transport from the supply chain reduced global warming potential by 18.8%. Compared with sugar on a sweetness equivalence basis, RA60 has approximately 5.7% to 10.2% the impact for global warming potential, 5.6% to 7.2% the impact for land use, and is lower across most other impact categories. Conclusion: This is the first LCA of steviol glycoside mix RA60 produced from leaf in Europe. The results indicate that RA60 can be used to reduce environmental impact of providing a sweet taste by replacing sugar across all impact categories. However, it is important to note that specific formulations in which RA60 is used will have a bearing on the final environmental impact of any food or beverage products. For solid foods, this requires further research. Supplementary Information: The online version contains supplementary material available at 10.1007/s11367-022-02127-9.

Differences in parental feeding styles and practices and toddler eating behaviour across complementary feeding methods: Managing expectations through consideration of effect size.

Nutritional experiences during infancy and toddlerhood influence the development of healthy eating habits later in life. Interest into solid food introduction practices has experienced resurgence due to the popularization of the baby-led weaning (BLW) approach as an alternative to more traditional parent-led weaning (PLW) practices. Although the literature shows beneficial effects of BLW on eating behaviours, the magnitude of those effects is unknown making parental expectation management challenging. This study provides an estimation of the size of the difference between the solid feeding practices groups for a variety of practices consistent with the development of healthy food preferences and behaviours. 565 participants with infants between 12 and 36 months old completed a survey concerning their preferred parental feeding styles, parental feeding practices, sources of information on feeding and toddler's eating behaviour. Participants were categorised to one of four groups reflecting the level of infant self-feeding level a month after the introduction of solid food (Strict PLW, Predominant PLW, Predominant BLW and Strict BLW). Estimated effect sizes of the observed significant differences showed that the magnitude of effects was modest to minimal. Moderate effect sizes were observed in comparisons regarding breastfeeding duration, maternal feeding practices, sources of information and types of first food given to the infants at the beginning of solid feeding introduction. When it comes to toddlers' eating behaviour and the family food environment, although some differences were statistically significant, the effect sizes were very small. Considering the long-lasting impact of food preferences developed at this stage along with the stress surrounding infant feeding decisions, it is crucial that the complementary feeding advice parents receive reflects realistic expectations of the outcomes regarding the effects on eating behaviour.

The development and validation of the Addiction-like Eating Behaviour Scale.

BACKGROUND: Overeating and obesity are frequently attributed to an addiction to food. However, there is currently a lack of evidence to support the idea that certain foods contain any specific addictive substance. An alternative approach is to focus on dimensions of observable behaviour, which may underpin a behavioural addiction to eating. To facilitate this, it is necessary to develop a tool to quantify addiction-like eating behaviour, which is not based on the clinical criteria for substance dependence. The current study provides initial validation of the Addiction-like Eating Behaviour Scale (AEBS). METHODS: English speaking male and female participants (N=511) from a community sample completed the AEBS, alongside a range of other health- and eating-related questionnaires including the Yale Food Addiction Scale (YFAS) and Binge Eating Scale (BES). Participants also provided their height and weight to enable calculation of body mass index (BMI). Finally, to assess test-retest reliability, an additional 70 participants completed the AEBS twice, 2 weeks apart. RESULTS: Principle components analysis revealed that a two-factor structure best accounted for the data. Factor 1 consisted of items that referred to appetitive drive, whereas factor two consisted of items that referred to dietary control practices. Both subscales demonstrated good internal reliability and test-retest reliability, and a confirmatory factor analysis confirmed the two-factor scale structure. AEBS scores correlated positively with body mass index (BMI) (P<0.001) and other self-report measures of overeating. Importantly, the AEBS significantly predicted variance in BMI above that accounted for by both the YFAS and BES (P=0.027). CONCLUSIONS: The AEBS provides a valid and reliable tool to quantify the behavioural features of a potential 'eating addiction'. In doing so, the AEBS overcomes many limitations associated with applying substance-dependence criteria to eating.

What have human experimental overfeeding studies taught us about adipose tissue expansion and susceptibility to obesity and metabolic complications?

Overfeeding experiments, in which we impose short-term positive energy balance, help unravel the cellular, physiological and behavioural adaptations to nutrient excess. These studies mimic longer-term mismatched energy expenditure and intake. There is considerable inter-individual heterogeneity in the magnitude of weight gain when exposed to similar relative caloric excess reflecting variable activation of compensatory adaptive mechanisms. Significantly, given similar relative weight gain, individuals may be protected from/predisposed to metabolic complications (insulin resistance, dyslipidaemia, hypertension), non-alcoholic fatty liver disease and cardiovascular disease. Similar mechanistic considerations underpinning the heterogeneity of overfeeding responses are pertinent in understanding emerging metabolic phenotypes, for example, metabolically unhealthy normal weight and metabolically healthy obesity. Intrinsic and extrinsic factors modulate individuals' overfeeding response: intrinsic factors include gender/hormonal status, genetic/ethnic background, baseline metabolic health and cardiorespiratory fitness; extrinsic factors include macronutrient (fat vs carbohydrate) content, fat/carbohydrate composition and overfeeding pattern. Subcutaneous adipose tissue (SAT) analysis, coupled with metabolic assessment, with overfeeding have revealed how SAT remodels to accommodate excess nutrients. SAT remodelling occurs either by hyperplasia (increased adipocyte number) or by hypertrophy (increased adipocyte size). Biological responses of SAT also govern the extent of ectopic (visceral/liver) triglyceride deposition. Body composition analysis by DEXA/MRI (dual energy X-ray absorptiometry/magnetic resonance imaging) have determined the relative expansion of SAT (including abdominal/gluteofemoral SAT) vs ectopic fat with overfeeding. Such studies have contributed to the adipose expandability hypothesis whereby SAT has a finite capacity to expand (governed by intrinsic biological characteristics), and once capacity is exceeded ectopic triglyceride deposition occurs. The potential for SAT expandability confers protection from/predisposes to the adverse metabolic responses to overfeeding. The concept of a personal fat threshold suggests a large inter-individual variation in SAT capacity with ectopic depot expansion/metabolic decompensation once one's own threshold is exceeded. This review summarises insight gained from overfeeding studies regarding susceptibility to obesity and related complications with nutrient excess.

The impact of hyperhidrosis on patients' daily life and quality of life: a qualitative investigation.

BACKGROUND: An understanding of the daily life impacts of hyperhidrosis and how patients deal with them, based on qualitative research, is lacking. This study investigated the impact of hyperhidrosis on the daily life of patients using a mix of qualitative research methods. METHODS: Participants were recruited through hyperhidrosis patient support groups such as the Hyperhidrosis Support Group UK. Data were collected using focus groups, interviews and online surveys. A grounded theory approach was used in the analysis of data transcripts. Data were collected from 71 participants, out of an initial 100 individuals recruited. RESULTS: Seventeen major themes capturing the impacts of hyperhidrosis were identified; these covered all areas of life including daily life, psychological well-being, social life, professional /school life, dealing with hyperhidrosis, unmet health care needs and physical impact. CONCLUSIONS: Psychosocial impacts are central to the overall impacts of hyperhidrosis, cutting across and underlying the limitations experienced in other areas of life.

Anterior cruciate ligament reconstruction and service in the British Army.

BACKGROUND: In 2005, British Army recruiting policy was revised to permit applicants with a history of anterior cruciate ligament reconstruction (ACLR) to be accepted for an initial period of engagement. AIMS: To determine whether personnel with an ACLR history are more likely to be medically discharged due to further injuries and complications than those without. METHODS: A retrospective study of personnel commissioned or enlisted into the British Army between January 2006 and July 2009. ACLR cases were identified from personnel and medical records and were age and sex matched to randomly selected controls. Reasons for discharge were identified. RESULTS: A total of 69 cases and 140 controls were included. A significant increase in risk of medical discharge was found in those with ACLR (incidence risk ratio was 3.04; 95% confidence interval 1.24-7.45). Sixty-one per cent of cases experienced complications linked to their previous surgery. CONCLUSIONS: The current British Army policy on recruitment of those with a history of ACLR should be reviewed in terms of fitness for service and risk of foreseeable harm in these individuals.

A molecular physiological review of vegetative desiccation tolerance in the resurrection plant Xerophyta viscosa (Baker).

MAIN CONCLUSION: Provides a first comprehensive review of integrated physiological and molecular aspects of desiccation tolerance Xerophyta viscosa. A synopsis of biotechnological studies being undertaken to improve drought tolerance in maize is given. Xerophyta viscosa (Baker) is a monocotyledonous resurrection plant from the family Vellociacea that occurs in summer-rainfall areas of South Africa, Lesotho and Swaziland. It inhabits rocky terrain in exposed grasslands and frequently experiences periods of water deficit. Being a resurrection plant it tolerates the loss of 95% of total cellular water, regaining full metabolic competency within 3 days of rehydration. In this paper, we review some of the molecular and physiological adaptations that occur during various stages of dehydration of X. viscosa, these being functionally grouped into early and late responses, which might be relevant to the attainment of desiccation tolerance. During early drying (to 55% RWC) photosynthesis is shut down, there is increased presence and activity of housekeeping antioxidants and a redirection of metabolism to the increased formation of sucrose and raffinose family oligosaccharides. Other metabolic shifts suggest water replacement in vacuoles proposed to facilitate mechanical stabilization. Some regulatory processes observed include increased presence of a linker histone H1 variant, a Type 2C protein phosphatase, a calmodulin- and an ERD15-like protein. During the late stages of drying (to 10% RWC) there was increased expression of several proteins involved in signal transduction, and retroelements speculated to be instrumental in gene silencing. There was induction of antioxidants not typically found in desiccation-sensitive systems, classical stress-associated proteins (HSP and LEAs), proteins involved in structural stabilization and those associated with changes in various metabolite pools during drying. Metabolites accumulated in this stage are proposed, inter alia, to facilitate subcellular stabilization by vitrification process which can include glass- and ionic liquid formation.

Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: a functional neuroimaging study.

BACKGROUND/OBJECTIVES: Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. SUBJECTS/METHODS: In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. RESULTS: Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). CONCLUSIONS: Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.

Potential benefits of satiety to the consumer: scientific considerations.

Foods and dietary patterns that enhance satiety may provide benefit to consumers. The aim of the present review was to describe, consider and evaluate research on potential benefits of enhanced satiety. The proposal that enhanced satiety could only benefit consumers by a direct effect on food intake should be rejected. Instead, it is proposed that there is a variety of routes through which enhanced satiety could (indirectly) benefit dietary control or weight-management goals. The review highlights specific potential benefits of satiety, including: providing appetite control strategies for consumers generally and for those who are highly responsive to food cues; offering pleasure and satisfaction associated with low-energy/healthier versions of foods without feeling 'deprived'; reducing dysphoric mood associated with hunger especially during energy restriction; and improved compliance with healthy eating or weight-management efforts. There is convincing evidence of short-term satiety benefits, but only probable evidence for longer-term benefits to hunger management, possible evidence of benefits to mood and cognition, inadequate evidence that satiety enhancement can promote weight loss, and no evidence on which consumers would benefit most from satiety enhancement. The appetite-reducing effects of specific foods or diets will be much more subtle than those of pharmaceutical compounds in managing hunger; nevertheless, the experience of pharmacology in producing weight loss via effects on appetite suggests that there is potential benefit of satiety enhancement from foods incorporated into the diet to the consumer.

Acute effects of a herb extract formulation and inulin fibre on appetite, energy intake and food choice.

The impact of two commercially available products, a patented herb extract Yerbe Maté, Guarana and Damiana (YGD) formulation and an inulin-based soluble fermentable fibre (SFF), alone or in combination, on appetite and food intake were studied for the first time in a double blind, placebo-controlled, cross-over design. 58 normal to slightly overweight women consumed a fixed-load breakfast followed 4h later by an ad libitum lunch. They were administered YGD (3 tablets) and SFF (5g in 100ml water), YGD and water (100ml), SFF and placebo (3 tablets) or water and placebo 15min before meals. Appetite was assessed using visual analogue scales, and energy intake was measured at lunch. Significant reductions in food intake and energy intake were observed when YGD was present (59.5g, 16.3%; 112.4kcal, 17.3%) and when SFF was present (31.9g, 9.1%; 80kcal, 11.7%) compared with conditions were products were absent. The lowest intake (gram and kcal) was in the YGD+SFF condition. Significant reductions in AUC hunger and AUC desire to eat were also observed after YGD+SFF combination. The data demonstrate that YGD produces a robust short-term effect on caloric intake, an effect augmented by SFF. Caloric compensation for SFF indicates independent effects on appetite regulation.

Hippocampal atrophy in temporal lobe epilepsy: the 'generator' and 'receiver'.

OBJECTIVE: Some patients with unilateral medial temporal lobe epilepsy (MTLE) display bilateral hippocampal atrophy on MRI, even though seizures originate in only one hippocampus. The correct identification of the epileptogenic hippocampus (the 'generator') vs the non-epileptogenic (the 'receiver') may lead to better surgical planning and results. MATERIALS AND METHODS: We studied 14 patients with MTLE (eight left and six right) who became seizure free after unilateral hippocampal resection, with hippocampal sclerosis confirmed by histology. Hippocampal tridimensional morphometry was performed comparing patients and healthy controls employing a voxel-wise Wilcoxon test. Results were corrected for multiple comparisons with the application of a False Discovery Rate (FDR)-corrected threshold for q < 0.05. RESULTS: Patients with MTLE showed atrophy involving the ipsilateral hippocampus and the contralateral hippocampus, more pronouncedly within the ipsilateral hippocampus in the anterior-inferior aspect of the hippocampal head (left MTLE, left hippocampus x = -28, y = -16, z = -24, Z = 3.6; right MTLE, right hippocampus x = 22, y = -11, z = -27, Z = 2.9). On the contralateral hippocampus, the atrophy was more noticeable in the posterior head and body areas. CONCLUSION: The epileptogenic hippocampal atrophy has an anatomically distinct pattern compared with the contralateral hippocampus. This information may help guide the presurgical assessment of MTLE.

Learning in lockdown: Using the COVID-19 crisis to teach children about food and climate change.

Food systems are significant sources of global greenhouse gas emissions (GHGE). Since emission intensity varies greatly between different foods, changing food choices towards those with lower GHGE could make an important contribution to mitigating climate change. Public engagement events offer an opportunity to communicate these multifaceted issues and raise awareness about the climate change impact of food choices. An interdisciplinary team of researchers was preparing food and climate change educational activities for summer 2020. However, the COVID-19 pandemic and lockdown disrupted these plans. In this paper, we report on shifting these events online over the month of June 2020. We discuss what we did and the reception to our online programme. We then reflect on and highlight issues that arose. These relate to: (1) the power dynamics of children, diet and climate change; (2) mental health, diet and COVID-19; (3) engaging the wider science, agriculture and food communities; (4) the benefits of being unfunded and the homemade nature of this programme; (5) the food system, STEAM (science, technology, engineering, arts and mathematics) and diversity; and (6) how our work fits into our ongoing journey of food and climate change education.

Ghrelin inhibits autonomic function in healthy controls, but has no effect on obese and vagotomized subjects.

OBJECTIVE: Ghrelin inhibits sympathetic nervous system (SNS) activity in rodents. We studied the effect of ghrelin on healthy humans, in obesity and in vagotomized subjects. DESIGN: Randomized, double-blinded, placebo-controlled crossover. SUBJECTS: Seven lean [mean body mass index (BMI) 23·6 ± 0·9 kg/m(2) ], seven morbidly obese (mean BMI 50·9 ± 4·4 kg/m(2) ) and seven post-gastrectomy subjects (mean BMI 22·0 ± 1·1 kg/m(2) ). MEASUREMENTS: Subjects were randomized to intravenous ghrelin (5 pmol/kg/min) or saline over 270 min. Subjects had a fixed calorie meal and a free choice buffet during the infusion. Heart rate variability (HRV) was measured. Total power (TP) represents overall autonomic function, low-frequency (LF) power represents sympathetic and parasympathetic activity, and high-frequency (HF) power represents parasympathetic activity. Very low (VLO) frequency represents the frequency band associated with thermogenesis. RESULTS: Preliminary anova analysis, looking at all three subject groups together, showed that ghrelin had an overall highly significant inhibitory effect on TP (P = 0·001), HF power (P = 0·04), VLO power (P = 0·03) and no effect on LF (P = 0·07). Further subset analysis revealed that ghrelin had a significant effect on TP (P = 0·03), borderline effect on LF power (P = 0·06) and no effect on HF power (P = 0·1) in healthy controls. By contrast in obese subjects, ghrelin had no effect on TP (P = 0·3), LF (P = 0·5) and HF (P = 0·06) and also no effect in the vagotomized subjects on TP (P = 0·7), LF (P = 0·7) and HF (P = 0·9). Ghrelin had no effect on the LF/HF ratio. CONCLUSIONS: Ghrelin inhibits SNS activity in healthy controls with a moderate effect on parasympathetic nervous system activity but had no effect on obese subjects. Vagotomized subjects also did not respond to ghrelin, suggesting the vagus nerve is important for the effects of peripheral ghrelin on the SNS.

Oral contraceptive effects on food choice during the follicular and luteal phases of the menstrual cycle. A laboratory based study.

Fifty-five women were recruited and assigned to a control group or an oral contraceptive (OC) use group. For the control groups menstrual cycle phase was determined using a menstrual calendar and only participants with regular cycles were recruited. Testing was carried out during a single day of the luteal and follicular phases, where participants were asked to consume and rate sweet and savoury snacks. Participants in the OC group were tested on the equivalent days of their pill calendar. In both groups, the luteal phase induced a greater caloric intake of sweet foods without altering hedonic ratings. No significant interactions between either phase or flavour with OC use on food intake or hedonic food ratings were found. At least for snack items, OC do not seem to alter the caloric intake fluctuations that occur during a normal menstrual cycle.

Ghrelin restores 'lean-type' hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects.

OBJECTIVE: To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects. DESIGN: A randomized, double-blind, placebo-controlled study. PATIENTS: Nine lean subjects (mean body mass index (BMI) 23.5+/-3 kg/m(2)) and nine morbidly obese subjects (mean BMI 51.4+/-10 kg/m(2)) and eight postgastrectomy subjects (mean BMI 22.4+/-1.0 kg/m(2)). INTERVENTIONS: Subjects were infused with either intravenous ghrelin (5 pmol kg(-1) min(-1)) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion. MAIN OUTCOME MEASURES: Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry. RESULTS: Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P<0.01) and obese subjects (35% increase, P=0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P<0.001). CONCLUSIONS: Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.

Chronic clozapine treatment in female rats does not induce weight gain or metabolic abnormalities but enhances adiposity: implications for animal models of antipsychotic-induced weight gain.

The ability of clozapine to induce weight gain in female rats was investigated in three studies with progressively lowered doses of clozapine. In an initial preliminary high dose study, clozapine at 6 and 12 mg/kg (i.p., b.i.d.) was found to induce weight loss. In a subsequent intermediate dose study, we obtained no evidence for clozapine-induced weight gain despite using identical procedures and doses of clozapine (1-4 mg/kg, i.p., b.i.d.) with which we have observed olanzapine-induced weight gain, hyperphagia, enhanced adiposity and metabolic changes [Cooper G, Pickavance L, Wilding J, Halford J, Goudie A (2005). A parametric analysis of olanzapine-induced weight gain in female rats. Psychopharmacology; 181: 80-89.]. Instead, clozapine induced weight loss without alteration in food intake and muscle mass or changes in levels of glucose, insulin, leptin and prolactin. However, these intermediate doses of clozapine enhanced visceral adiposity and elevated levels of adiponectin. In a final study, low doses of clozapine (0.25-0.5 mg/kg, i.p, b.i.d.) induced weight loss. These data demonstrate that clozapine-induced weight gain can be much more difficult to observe in female rats than olanzapine-induced weight gain. Moreover, these findings contrast with clinical findings with clozapine, which induces substantial weight gain in humans. Clozapine-induced enhanced adiposity appears to be easier to observe in rats than weight gain. These findings, along with other preclinical studies, suggest that enhanced adiposity can be observed in the absence of antipsychotic-induced weight gain and hyperphagia, possibly reflecting a direct drug effect on adipocyte function independent of drug-induced hyperphagia [e.g. Minet-Ringuet J, Even P, Valet P, Carpene C, Visentin V, Prevot D, Daviaud D, Quignard-Boulange A, Tome D, de Beaurepaire R (2007). Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. Molecular Psychiatry; 12: 562-571.]. These and other findings which show that the results of studies of antipsychotic treatment in animals do not always mimic clinical findings have important implications for the use of animal models of antipsychotic-induced weight gain. With regard to weight gain the results obtained appear to depend critically on the experimental procedures used and the specific drugs studied. Thus such models are not without limitations. However, they do consistently demonstrate the ability of various antipsychotics to enhance adiposity.