Glucagon-like peptide 1 (GLP-1).

BACKGROUND: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent ß-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity. SCOPE OF REVIEW: In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases. MAJOR CONCLUSIONS: Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders.

Impaired nutritional status in geriatric trauma patients.

BACKGROUND/OBJECTIVES: Malnutrition is an established risk factor for adverse clinical outcomes. Our aim was to assess nutritional status among geriatric trauma patients. SUBJECTS/METHODS: We enrolled 169 consecutive patients (⩾70 years) admitted to the Geriatric Traumatology Centre (University Hospital Zurich, Switzerland). On admission to acute care, nutritional status was assessed with the mini nutritional assessment (score<17=malnourished (M), ⩽23.5=at risk of malnutrition (ARM), >23.5=normal). At the same examination, we assessed mental (Geriatric Depression Scale; GDS) and cognitive function (Mini-Mental State Examination; MMSE), frailty status (Fried Scale), and number of comorbidities and medications. Further, discharge destination was documented. All analyses were adjusted for age and gender. RESULTS: A total of 7.1% of patients were malnourished and 49.1% were ARM. Patients with reduced mental health (GDS⩾5: 30.5 vs 11.5%; P=0.004), impaired cognitive function (MMSE⩽26: 23.6±0.5 vs 26.0±0.6; P=0.004), prevalent frailty (32.5 vs 8%; P<0.001), more comorbidities (2.3±0.1 vs 1.3±0.2; P<0.0001) and medications (5.6±0.3 vs 3.4±0.4; P<0.0001) were more likely to have an impaired nutritional status (M+ARM). Further, M+ARM patients were twice as likely to be discharged to destinations different to home (odds ratio=2.08; confidence interval 1.07-4.05). CONCLUSIONS: In this consecutive sample of geriatric trauma patients, 56.2% had an M+ARM upon admission to acute care, which was associated with indicators of worse physical, mental and cognitive health and predicted a more than twofold greater odds of being discharged to a destination other than home.

Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency.

Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN+ cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.

Intestinal GLP-1 and satiation: from man to rodents and back.

In response to luminal food stimuli during meals, enteroendocrine cells release gastrointestinal (GI) peptides that have long been known to control secretory and motor functions of the gut, pancreas and liver. Glucagon-like peptide-1 (GLP-1) has emerged as one of the most important GI peptides because of a combination of functions not previously ascribed to any other molecule. GLP-1 potentiates glucose-induced insulin secretion, suppresses glucagon release, slows gastric emptying and may serve as a satiation signal, although the physiological status of the latter function has not been fully established yet. Here we review the available evidence for intestinal GLP-1 to fulfill a number of established empirical criteria for assessing whether a hormone inhibits eating by eliciting physiological satiation in man and rodents.

Abnormal context-reward associations in an immune-mediated neurodevelopmental mouse model with relevance to schizophrenia.

Impairments in central reward processing constitute an important aspect of the negative symptoms of schizophrenia. Despite its clinical relevance, the etiology of deficient reward processing in schizophrenia remains largely unknown. Here, we used an epidemiologically informed mouse model of schizophrenia to explore the effects of prenatal immune activation on reward-related functions. The model is based on maternal administration of the viral mimic PolyI:C and has been developed in relation to the epidemiological evidence demonstrating enhanced risk of schizophrenia and related disorders following prenatal maternal infection. We show that prenatal immune activation induces selective deficits in the expression (but not acquisition) of conditioned place preference for a natural reward (sucrose) without changing hedonic or neophobic responses to the reward. On the other hand, prenatal immune activation led to enhanced place preference for the psychostimulant drug cocaine, while it attenuated the locomotor reaction to the drug. The prenatal exposure did not alter negative reinforcement learning as assessed using a contextual fear conditioning paradigm. Our findings suggest that the nature of reward-related abnormalities following prenatal immune challenge depends on the specificity of the reward (natural reward vs drug of abuse) as well as on the valence domain (positive vs negative reinforcement learning). Moreover, our data indicate that reward abnormalities emerging in prenatally immune-challenged offspring may, at least in part, stem from an inability to retrieve previously established context-reward associations and to integrate such information for appropriate goal-directed behavior.

Enterocyte-afferent nerve interactions in dietary fat sensing.

The central nervous system (CNS) constantly monitors nutrient availability in the body and, in particular, in the gastrointestinal (GI) tract to regulate nutrient and energy homeostasis. Extrinsic parasympathetic and sympathetic nerves are crucial for CNS nutrient sensing in the GI tract. These extrinsic afferent nerves detect the nature and amount of nutrients present in the GI tract and relay the information to the brain, which controls energy intake and expenditure accordingly. Dietary fat and fatty acids are sensed through various direct and indirect mechanisms. These sensing processes involve the binding of fatty acids to specific G protein-coupled receptors expressed either on the afferent nerve fibres or on the surface of enteroendocrine cells that release gut peptides, which themselves can modulate afferent nerve activity through their cognate receptors or have endocrine effects directly on the brain. Further dietary fat sensing mechanisms that are related to enterocyte fat handling and metabolism involve the release of several possible chemical mediators such as fatty acid ethanolamides or apolipoprotein A-IV. We here present evidence for yet another mechanism that may be based on ketone bodies resulting from enterocyte oxidation of dietary fat-derived fatty acids. The presently available evidence suggests that sympathetic rather than vagal afferents are involved, but further experiments are necessary to critically examine this concept.

High dietary fat intake influences the activation of specific hindbrain and hypothalamic nuclei by the satiety factor oleoylethanolamide.

Chronic exposure to a diet rich in fats changes the gastrointestinal milieu and alters responses to several signals involved in the control of food intake. Oleoylethanolamide (OEA) is a gut-derived satiety signal released from enterocytes upon the ingestion of dietary fats. The anorexigenic effect of OEA, which requires intestinal PPAR-alpha receptors and is supposedly mediated by vagal afferents, is associated with the induction of c-fos in several brain areas involved in the control of food intake, such as the nucleus of the solitary tract (NST) and the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). In the present study we investigated whether the exposure to a high fat diet (HFD) alters the hindbrain and hypothalamic responses to OEA. To this purpose we evaluated the effects of OEA at a dose that reliably inhibits eating (10mg/kg i.p.) on the induction of c-fos in the NST, area postrema (AP), PVN and SON in rats maintained either on standard chow or a HFD. We performed a detailed analysis of the different NST subnuclei activated by i.p. OEA and found that peripheral OEA strongly activates c-fos expression in the AP, NST and in the hypothalamus of both chow and HFD fed rats. The extent of c-fos expression was, however, markedly different between the two groups of rats, with a weaker activation of selected NST subnuclei and stronger activation of the PVN in HFD-fed than in chow-fed rats. HFD-fed rats were also more sensitive to the immediate hypophagic action of OEA than chow-fed rats. These effects may be due to a decreased sensitivity of vagal afferent fibers that might mediate OEA's actions on the brain and/or an altered sensitivity of brain structures to OEA.

Vagal afferents mediate early satiation and prevent flavour avoidance learning in response to intraperitoneally infused exendin-4.

Glucagon-like peptide-1 receptor (GLP-1R) agonists such as exendin-4 (Ex-4) affect eating and metabolism and are potential candidates for treating obesity and type II diabetes. In the present study, we tested whether vagal afferents mediate the eating-inhibitory and avoidance-inducing effects of Ex-4. Subdiaphragmatic vagal deafferentation (SDA) blunted the short-term (< 1 h) but not long-term eating-inhibitory effect of i.p.-infused Ex-4 (0.1 µg/kg) in rats. A dose of 1 µg/kg Ex-4 reduced 0.5, 1, 2 and 4 h cumulative food intake in SDA and sham-operated rats to a similar extent. Paradoxically, SDA but not sham rats developed a conditioned flavour avoidance (CFA) after i.p. Ex-4 (0.1 µg/kg). SDA completely blunted the induction of c-Fos expression by Ex-4 in the hypothalamic paraventricular nucleus. Ex-4, however, increased the number of c-Fos expressing cells, independent of intact vagal afferents, in the nucleus accumbens and in the central nucleus of the amygdala, the lateral external parabrachial nucleus, the caudal ventrolateral medulla and the dorsal vagal complex. These data suggest that intact vagal afferents are only necessary for the full expression of the early satiating effect of Ex-4 but not for later eating-inhibitory actions, when circulating Ex-4 might reach the brain via the circulation. Our data also dissociate the satiating and avoidance-inducing effects of the low Ex-4 dose tested under our conditions and suggest that vagal afferent signalling may protect against the development of CFA. Taken together, these findings reveal a complex role of vagal afferents in mediating the effects of GLP-1R activation on ingestive behaviour.

Hepatic-portal vein infusions of glucagon-like peptide-1 reduce meal size and increase c-Fos expression in the nucleus tractus solitarii, area postrema and central nucleus of the amygdala in rats.

We recently reported that brief, remotely controlled intrameal hepatic-portal vein infusions of glucagon-like peptide-1 (GLP-1) reduced spontaneous meal size in rats. To investigate the neurobehavioural correlates of this effect, we equipped male Sprague-Dawley rats with hepatic-portal vein catheters and assessed (i) the effect on eating of remotely triggered infusions of GLP-1 (1 nmol/kg, 5 min) or vehicle during the first nocturnal meal after 3 h of food deprivation and (ii) the effect of identical infusions performed at dark onset on c-Fos expression in several brain areas involved in the control of eating. GLP-1 reduced (P < 0.05) the size of the first nocturnal meal and increased its satiety ratio. Also, GLP-1 increased (P < 0.05) the number of c-Fos-expressing cells in the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala, but not in the arcuate or paraventricular hypothalamic nuclei. These data suggest that the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala play a role in the eating-inhibitory actions of GLP-1 infused into the hepatic-portal vein; it remains to be established whether activation of these brain nuclei reflect satiation, aversion, or both.

Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii.

To determine whether Toxoplasma gondii infection could modify biological phenomena associated with brain ischemia, we investigated the effect of permanent middle cerebral artery occlusion (MCAO) on neuronal survival, inflammation and redox state in chronically infected mice. Infected animals showed a 40% to 50% decrease of infarct size compared with non-infected littermates 1, 4 and 14 days after MCAO. The resistance of infected mice may be associated with increased basal levels of anti-inflammatory cytokines and/or a marked reduction of the MCAO-related brain induction of two pro-inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma (IFNgamma). In addition, potential anti-inflammatory/neuroprotective factors such as nerve growth factor, suppressor of cytokine signaling-3, superoxide dismutase activity, uncoupling protein-2 and glutathione (GSH) were upregulated in the brain of infected mice. Consistent with a role of GSH in central cytokine regulation, GSH depletion by diethyl maleate inhibited Toxoplasma gondii lesion resistance by increasing the proinflammatory cytokine IFNgamma brain levels. Overall, these findings indicate that chronic toxoplasmosis decisively influences both the inflammatory molecular events and outcome of cerebral ischemia.

Evidence for different nutrient partitioning in Boran (Bos indicus) and Boran x Holstein cows when re-allocated from low to high or from high to low feeding level.

This study tested the hypothesis that purebred Boran (Bos indicus) cows and crossbreds of Boran and Holstein respond differently to long-term changes of feeding level in nutrient partitioning to milk and body fat stores. A total of 27 cows of these two genotypes were subjected either to a low or a high feeding level from their first oestrus as heifers until birth of their third calf. Half of the cows of each genotype were then switched to the other feeding level during the third reproduction cycle. If at all, Boran cows responded to a change in the feeding level almost exclusively by a corresponding change in body weight but not milk yield. Crossbred cows kept continuously on the low feeding level had a lower milk yield than those continuously fed the high level, but lost similar amounts of body weight. In crossbred cows, changing the feeding level from high to low was accompanied by a mobilization of body reserves, whereas a change from low to high level resulted mostly in an increase in milk yield. Certain other genotype differences in metabolic response were obvious from differences in body composition and from the metabolic profile either reflected in blood (particularly insulin-like growth factor I) or in adipose tissue (lipoprotein lipase). Reproductive performance differed between genotypes, with shorter lactations associated with earlier occurrences of the first oestrus in the Boran cows. Generally, feeding history appeared to have at least as much influence on energy partitioning as the actual feeding level. In conclusion, purebred Boran cows seem to react to long-term food fluctuations mainly by mobilizing and restoring body fat reserves, whereas cows crossbred with Holstein tend to spend extra energy preferentially for milk production.

In vitro screening of six anthelmintic plant products against larval Haemonchus contortus with a modified methyl-thiazolyl-tetrazolium reduction assay.

Because of the increasing anthelmintic resistance and the impact of conventional anthelmintics on the environment, it is important to look for alternative strategies against gastrointestinal nematodes. Phytotherapy could be one of the major options to control these pathologies. Extracts or ingredients of six different plant species were tested against exsheathed infective larvae of Haemonchus contortus using a modified methyl-thiazolyl-tetrazolium (MTT) reduction assay. Pyrantel tartrate was used as reference anthelmintic. Bromelain, the enzyme complex of the stem of Ananas comosus (Bromeliaceae), the ethanolic extracts of seeds of Azadirachta indica (Meliaceae), Caesalpinia crista (Caesalpiniaceae) and Vernonia anthelmintica (Asteraceae), and the ethanolic extracts of the whole plant of Fumaria parviflora (Papaveraceae) and of the fruit of Embelia ribes (Myrsinaceae) showed an anthelmintic efficacy of up to 93%, relative to pyrantel tartrate. Based on these results obtained with larval Haemonchus contortus, the modified MTT reduction assay could be a possible method for testing plant products with anthelmintic properties.

Acute and chronic administration of immunomodulators induces anorexia in Zucker rats.

To investigate the possible involvement of leptin signaling in lipopolysaccharide (LPS) anorexia, we compared the anorectic effect of LPS in genetically obese (fa/fa) Zucker rats and in their lean (Fa/?) counterparts. The effects of interleukin-1beta (IL-1beta) and muramyl dipeptide (MDP) were also tested. LPS [100 microg/kg body weight (BW)], IL-1beta (2 microg/kg BW) and MDP (2.2 mg/kg BW) injected intraperitoneally (i.p.) at lights out reduced food intake similarly in obese and lean rats. LPS injection at 500 or 1000 microg/kg BW (i.p.) also reduced food intake and BW similarly in obese and lean rats, but obese regained BW faster than lean rats. LPS (2.45 microg or 9.8 microg/h/rat) administered chronically with i.p. implanted osmotic pumps reduced food intake similarly on experimental day 1, regardless of the genotype. After day 3, the lean rats' anorectic response and recovery were dose-dependent, whereas the anorectic response in obese rats was minimally affected by dose (significant dose effect only on day 3). Again, obese rats regained lost BW faster than lean rats. These results do not support a role for leptin as the sole mediator of anorexia induced by bacterial products (LPS and MDP) and IL-1beta.

Role for CD14, TLR2, and TLR4 in bacterial product-induced anorexia.

The cell surface component CD14 and the toll-like receptors 2 and 4 (TLR2 and TLR4) are important in mediating the immune responses to bacterial products in mammals. Using mice genetically deficient in CD14, TLR2, or TLR4, we studied the role of these molecules in the anorectic effects of LPS and muramyl dipeptide (MDP). CD14 or TLR2 knockout (KO) and TLR4-deficient (TLR4-DEF) mice as well as corresponding wild-type (WT) colittermates were injected intraperitoneally at dark onset with LPS (2 microg/mouse), MDP (10 mg/kg), interleukin-1 beta (IL-1 beta, 150 ng/mouse), or vehicle, and food intake was recorded. LPS and MDP reduced food intake in WT mice of all genotypes tested. The anorectic effect of LPS was attenuated (P < 0.04) in CD14-KO and TLR4-DEF mice but not in TLR2-KO (P > 0.05). The anorectic effect of MDP was blunted in CD14-KO and TLR2-KO (P < 0.02) mice but not in TLR4-DEF mice. IL-1 beta reduced food intake similarly in all genotypes tested. These results indicate that CD14 is involved in mediating the anorectic effects of both LPS and MDP. Furthermore, TLR4 and TLR2 are specifically involved in mediating the anorectic effects of LPS and MDP, respectively. The results are consistent with the hypothesis that TLR4 functions as the true LPS receptor and that TLR2 is involved in recognition of gram-positive bacterial products.

The anthelmintic efficacy of five plant products against gastrointestinal trichostrongylids in artificially infected lambs.

Forty-eight helminth-free lambs were divided into eight groups (A-H) of six animals. Groups A-G were infected artificially with 10,000 third stage larvae of Haemonchus contortus and 20,000 third stage larvae of Trichostrongylus colubriformis, whereas group H remained uninfected. Thirty days post-infection the lambs were treated orally with a single dosage of one of the following products: group A with 3 mg/kg body weight (BW) of an aqueous ethanol extract (70%, v/v) of the seeds of Azadirachta indica A. Juss syn. Melia azedarach L. (Meliaceae); group B with 1 g/kg BW of a raw powder of the leaves of Ananas comosus (L.) Merr. (Bromeliaceae); group C with 0.3 mg/kg BW of an aqueous ethanol extract of a 1:1 mixture (g/g) of Vernonia anthelmintica (L.) Willd. (Asteraceae) seeds and Embelia ribes Burm (Myrsinaceae) fruits; group D with 183 mg/kg BW of an aqueous ethanol extract of the whole plants of Fumaria parviflora Lam. (Fumariaceae); group E with 28 mg/kg BW of an aqueous ethanol extract of the seeds of Caesalpinia crista L. (Caesalpiniaceae); group F with 25 mg/kg BW of pyrantel tartrate and group G with 50% ethanol. Group H remained untreated. Only the ethanol extract of F. parviflora caused a strong reduction of the faecal egg counts (100%) and a 78.2 and 88.8% reduction of adult H. contortus and T. colubriformis on day 13 post-treatment. The extract was as effective as the reference compound pyrantel tartrate. Therefore, the ethanol extract itself or single constituents of F. parviflora could be a promising alternative source of anthelmintic for the treatment of gastrointestinal trichostrongylids in small ruminants.

A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats.

Because nonselective cycloooxygenase (COX) inhibition attenuated anorexia after lipopolysaccharide (LPS) administration, we tested the ability of resveratrol (2.5, 10, and 40 mg/kg) and NS-398 (2.5, 10, and 40 mg/kg), selective inhibitors of the two COX isoforms COX-1 and -2, respectively, to attenuate LPS (100 microg/kg ip)-induced anorexia. NS-398 (10 and 40 mg/kg) administered with LPS at lights out attenuated LPS-induced anorexia, whereas resveratrol at all doses tested did not. Because prostaglandin (PG) E(2) is considered the major metabolite synthesized by COX, we measured plasma and cerebrospinal fluid (CSF) PGE(2) levels after LPS administration. LPS induced a time-dependent increase of PGE(2) in CSF but not in plasma. NS-398 (5, 10, and 40 mg/kg) blocked the LPS-induced increase in CSF PGE(2), whereas resveratrol (10 mg/kg) did not. These results support a role of COX-2 in mediating the anorectic response to peripheral LPS and point at PGE(2) as a potential neuromodulator involved in this response.

Role of bovine chemokines produced by dendritic cells in respiratory syncytial virus-induced T cell proliferation.

Respiratory syncytial virus (RSV) has been reported to induce the production of chemokines in the airway epithelia. Dendritic cells (DC) are the most potent antigen-presenting cells. They are located throughout the body and release chemokines in response to inflammation and infection. We have investigated the chemokine profile of bovine DC in response to exposure to bovine RSV (BRSV). Transcripts for several chemokines were detected by RT-PCR, subsequently cloned and expressed, and the products analysed by western blotting. To test the effect of the recombinant chemokines on RSV-induced T cell proliferation, DC were pulsed with BRSV, irradiated, and added to purified bovine CD4(+) T cells from RSV-immune cattle in combination with various concentrations of recombinant chemokines, and the proliferative response of the T cells assessed. Eotaxin was the only chemokine, of those investigated, that specifically enhanced the T cell response to BRSV-pulsed DC. Addition of MIP-1alpha to control wells or to wells containing BRSV-pulsed DC had similar effects, suggesting non-specific stimulation of T cells. RANTES and MIP-3alpha did not seem to influence the proliferative response of T cells co-cultured with BRSV-pulsed DC. Thus, although BRSV induced the production of several chemokines by DC, only eotaxin promoted a BRSV specific CD4(+) T cell proliferative response.

Morphologic and functional changes in bovine monocytes infected in vitro with the bovine leukaemia virus.

Experiments on the host cell spectrum of bovine leukaemia virus (BLV), a retrovirus closely related to the human T-cell leukaemia virus (HTLV), have yielded conflicting data. Currently, BLV is known to infect B cells, whereas its ability to infect other cell types, e.g. monocytes/macrophages, is doubtful. As monocytes/macrophages may have profound effects on the diversity of the T-cell response, we studied the possibility of in vitro infection, using bovine monocytes and SV40-transformed bovine macrophages. Proviral DNA was detected by nested polymerase chain reaction (PCR) from day 1 until the end of the experiments at either day 5 or day 80, depending on the quantity of virus used for infection. In addition, the infection was associated with morphological changes in infected cells as revealed by electron microscopy. The in vitro infection did not significantly change either the expression of surface antigens (CD11b, CD32, and major histocompatibility complex (MHC) class II) or the amounts of cytokine transcripts (interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, IL-6 and IL-12p40) with or without lipopolysaccharide (LPS) stimulation. The data suggest that BLV can infect monocytes, but the infection does not seem to influence the function or the phenotype of these cells. Infected monocytes may, however, play a role as a viral reservoir in vivo.

Effect of hydroxycitrate on food intake and body weight regain after a period of restrictive feeding in male rats.

We examined whether dietary supplementation of hydroxycitrate (HCA), a competitive inhibitor of the extramitochondrial enzyme ATP-citrate-lyase, which inhibits lipogenesis, reduces food intake and body weight regain in rats after 10-15% weight loss. In four experiments, 24 male rats were fed restrictively (10 g/day) for 10 days and then given ad lib access to one of four different diets (HI-Suc=high sucrose; HI-Glu=high glucose; Chow=grounded standard rat chow; HI-Glu+Fat=high glucose+fat) varying in the content of fat and low molecular carbohydrates for the following 10 days. For half of the rats (n=12), the ad lib diet was supplemented with 3% (w/w) HCA. HCA reduced body weight regain with all diets except Chow. HCA also reduced food intake temporarily with three of the four tested diets. The suppressive effect of HCA on food intake was particularly strong with the HI-Glu+Fat diet (fat=24% of energy). With Diet HI-Glu and HI-Glu+Fat HCA reduced the feed conversion efficiency (cumulative body weight regain (g)/cumulative food intake (MJ)) during the 10 ad lib days, suggesting that it also increased energy expenditure. This effect seemed to be positively related to the glucose content of the diet. All in all, HCA reduced body weight regain after substantial body weight loss, and the effects are presumably linked to its inhibiting effect on lipogenesis, but the exact mechanism still has to be determined.