Ventromedial Hypothalamic Lesions Research Articles

Role of Ventromedial Hypothalamus in Sucrose-Induced Obesity on Metabolic Parameters.

Background:Obesity is because of excessive fat accumulation that affects health adversely in the form of various diseases such as diabetes, hypertension, cardiovascular diseases, and many other disorders. Our Indian diet is rich in carbohydrates, and hence the sucrose-induced obesity is an apt model to mimic this. Ventromedial hypothalamus (VMH) is linked to the regulation of food intake in animals as well as humans.Purpose:To understand the role of VMHin sucrose-induced obesity on metabolic parameters.Methods:A total of 24 adult rats were made obese by feeding them on a 32% sucrose solution for 10 weeks. The VMH nucleus was ablated in the experimental group and sham lesions were made in the control group. Food intake, body weight, and biochemical parameters were compared before and after the lesion.Results:Male rats had a significant weight gain along with hyperphagia, whereas female rats did not have a significant weight gain inspite of hyperphagia. Insulin resistance and dyslipidemia were seen in both the experimental and control groups.Conclusion:A sucrose diet produces obesity which is similar to the metabolic syndrome with insulin resistance and dyslipidemia, and a VMH lesion further exaggerates it. Males are more prone to this exaggeration.

Obesity can alter energetic responses to food restriction

Reduction in energy expenditure during fasting and chronic food restriction is well known and represents a mechanism of energy conservation, sparing energy, and preventing excessive weight and energy loss. The present study aimed to investigate if obesity can alter the reduction in energy expenditure that occurs in response to chronic food restriction, using two different experimental models that promote distinct types of obesity. Female Wistar rats were submitted to two models of obesity: hypercaloric diet ingestion (HD) and bilateral lesion of ventromedial hypothalamus (VMHL). Thirty days after the beginning of each treatment (HD and VMHL), the control and obese animals were subdivided in two groups that ingested for 30 days ad libitum diet or 50% of food ingested by the respective ad libitum group (control or obese). At the end of this period, the animals were euthanized, and the energy balance and body composition were determined. Obese animals (HD and VMHL) showed increase on their body fat, confirming the effectiveness of the models in obesity development. When submitted to food restriction, control and obese animals showed a significant reduction in body weight and energy, metabolizable energy intake, energy expenditure, gross food efficiency, and body fat content, when compared with their respective ad libitum groups. Energy expenditure reduction shown by obese food-restricted animals for both models was significantly lower than the one shown by non-obese food-restricted groups. Obesity reduces the “sparing of energy” in food-restricted animals, suggesting that fat availability is one of the modulators of this mechanism; moreover, this physiologic adaptation should be considered in clinical nutrition protocols.

Gene Expression Analysis in Rat Pancreas Observed with Whole-Transcript Exon Array after Ventromedial Hypothalamic Lesions

Background: It was reported previously that using Affymetrix Rat Genome 230 2.0, one of a class of standard 3′ based arrays, ventromedial hypothalamic (VMH) lesions affected the expressions of cell proliferation-related genes, neuron-related genes, and metabolism-related genes. The released Affymetrix Rat Gene 1.0 ST array has 2 major differences compared with standard 3′ based arrays, including Rat Genome 230 2.0: it interrogates the entire mRNA transcript and uses DNA targets. Purpose: This study is aimed at assessing the impact of these differences on the array performance. Methods: The study used Rat Gene 1.0 ST array, one of a class of whole-transcript rat exon arrays to examine the cellular mechanisms of gene regulation in the rat pancreas after VMH lesions. Results: Although the results showed that VMH lesions regulated genes involved in enzymes, metabolism, transport, binding differentiation, migration, morphology, apoptosis, neuron and immunity, the probes identified by these 2 arrays were remarkably different. Conclusion: This study also confirmed that VMH lesions may affect the expression of many functional genes in rat pancreas.

Abnormal feeding behaviour in spinalised rats is mediated by hypothalamus: Restorative effect of exposure to extremely low frequency magnetic field.

Experimental study. To investigate the role of hypothalamus in abnormal feeding behaviour after spinal cord injury (SCI) and the effect of exposure to extremely low frequency magnetic field (ELF-MF) on it. India. Male Wistar rats (n=44) were divided into Sham (laminectomy), SCI (complete transection of T13 spinal cord), SCI+MF (ELF-MF exposure to SCI rats), VMHL (lesion of ventromedial hypothalamus; VMH), SCI+VMHL (VMHL after SCI) and SCI+VMHL+MF (ELF-MF exposure to SCI+VMHL rats) groups. Food intake (FI), water intake (WI), calorie intake (CI), body weight (BWT), taste preference and sucrose-induced biphasic (SIB) response to noxious stimulus were studied pre and post surgery. Neuronal activity at VMH was assessed by c-Fos immunohistochemistry. The extent of neuronal degeneration and regeneration in spinal cord was assessed microscopically. Data revealed post-SCI decrease in FI, WI, CI and BWT, preference for sodium chloride and citric acid, prolonged analgesic phase of SIB and increased c-Fos immunoreactivity in VMH of SCI rats vs Sham rats. VMH lesion increased FI, WI, CI, BW, preference for sweet tastants and abolished SIB, whereas in SCI+VMHL rats it abolished the effects of SCI on these parameters indicating probable involvement of VMH in SCI-induced alteration in feeding behaviour. Exposure to MF improved the study parameters in SCI rats and reduced the c-Fos immunoreactivity in VMH besides reduction in lesion volume, greater myelination and neuronal regeneration at SCI site. SCI influences VMH, leading to alteration in feeding behaviour, which is improved by exposure to ELF-MF.

Comparison of the effect of lesions of ventromedial hypothalamus and posterodorsal amygdala on body weight and immunological parameters in albino Wistar rats

Background and Aim: Although hypothalamic and extrahypothalamic areas are known to influence food intake (FI), body weight (BW) and immunity, the exact nature and magnitude of alteration following lesion of these areas have not adequately studied. Therefore, the present study was aimed at comparing the effect of lesions of ventromedial hypothalamus (VMH) and posterodorsal amygdala (PDA) on FI, BW gain and immunological parameters in albino Wistar rats. Methods: A total of 48 albino Wistar rats were taken for the study and were divided equally into VMH group and PDA group with 12 control and 12 experimental rats in each. Bilateral electrolytic lesion of the respective nuclei was performed by stereotaxy. The pre- and post-lesion parameters of both groups were compared. Results: The percentage increase in FI and BW gain was significantly less ( P P P P Conclusion: The above-mentioned findings suggest that the role of VMH on feeding is more pronounced than PDA, indicating that VMH has a stronger regulation of adiposity than PDA. Though VMH and PDA are involved in the regulation of immune functions, VMH has a stronger control over immune functions than PDA. Hence, VMH has greater control over adiposity, feeding behavior, and immune functions than PDA.

Ventromedial hypothalamic lesions downregulate multiple immune signaling pathways in rat pancreatic islets

It was recently reported that ventromedial hypothalamic lesions change the expression of cell proliferation-related genes and metabolism-related genes in rat pancreatic islets. This study has examined how gene families involved in immune responses are regulated in rat pancreatic islets after VMH lesions formation. Total pancreatic islets RNA was extracted, and differences in the gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH-lesioned rats were investigated using DNA microarray and real-time polymerase chain reaction. VMH lesions downregulated multiple immune signaling pathways in rat pancreatic islets. Real-time polymerase chain reaction also confirmed that gene expressions of RT1 class II, locus Bb (RT1-Bb) was up-regulated and Spi-B transcription factor (Spib) was downregulated at day 3 after the VMH lesions. Ventromedial hypothalamic lesions may change the expression of multiple immune response genes in rat pancreatic islets.

Changes of the expressions of multiple metabolism genes in rat pancreatic islets after ventromedial hypothalamic lesioning

It was recently reported that ventromedial hypothalamic lesions change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets. This study has examined how gene families involved in metabolism are regulated in rat pancreatic islets after VMH lesions formation. Total pancreatic islets RNA was extracted, and differences in the gene expression profiles between rats at day 3 after VMH lesioning and sham–VMH-lesioned rats were investigated using DNA microarray and real-time polymerase chain reaction. The VMH lesions regulated the genes that are involved in functions related to metabolism in the pancreas islets. Real-time polymerase chain reaction also confirmed that gene expressions of arachidonate 15-lipoxygenase (Alox15) was up-regulated and pancreatic lipase (Pnlip) was downregulated at day 3 after the VMH lesions. Ventromedial hypothalamic lesions may change the expression of multiple metabolism genes in rat pancreatic islets.

Ventromedial hypothalamic lesions change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets

Studies in normal rats and ob/ob mice indicated that islet neogenesis does not occur in the intact rodent pancreas. We previously reported that ventromedial hypothalamic (VMH) lesions stimulated cell proliferation of rat pancreatic islet B and acinar cells primarily through a cholinergic receptor mechanism and examined how gene families involved in cell proliferation in total pancreatic tissue are regulated after VMH lesions formation. This study examined how gene families involved in cell proliferation in pancreatic islets alone are regulated after VMH lesions formation. Pancreatic islet RNA was extracted, and differences in gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH-lesioned rats were investigated using DNA microarray and real-time polymerase chain reaction. VMH lesions regulated genes that were involved in functions related to cell cycle and differentiation, growth, binding, apoptosis and morphology in pancreas islets. Real-time polymerase chain reaction also confirmed that gene expression of polo-like kinase 1 (Plk1) and topoisomerase (DNA) II α 170 kDa (Top2a), and stanniocalcin 1 (Stc1) were upregulated at day 3 after the VMH lesions. Ventromedial hypothalamic lesions may change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets.

Role of Ventromedial hypothalamus in high fat diet induced obesity in male rats: association with lipid profile, thyroid profile and insulin resistance.

Ventromedial hypothalamus (VMH) plays a major role in food intake, obesity and energy homeostasis. There is a report of gender difference in energy balance with increased vulnerability of males to cardiac disease. Body metabolism is greatly influenced by the diet we eat and some of the blood parameters like plasma glucose, insulin, lipid profile and thyroid profile depict a picture of energy homeostasis of the body. The present study was conducted to assess the effect of VMH in high fat diet (HFD) induced obesity and its link with insulin, glucose, thyroid and lipid profile of male Wistar rats. The male rats (n = 12) were given HFD for a period of 10 weeks to induce obesity. After obtaining a basal recording of food intake, body weight, glucose, insulin, thyroid and lipid profile, animals were divided into control and experimental group (n = 6 male in each). Experimental rats underwent electrolytic ablation of VMH whereas control rats underwent sham lesion. A post-lesion recording was taken at the end of four weeks. The rats had a greater food intake and more body weight gain after HFD schedule in both the groups. After VMH lesion, food intake increased further, only in experimental group. Plasma glucose, Insulin, HOMA - IR, total cholesterol (TC) and triglycerides (TG) were significantly increased compared to the pre-lesion values in experimental group (P<0.001). Ten week of HFD resulted in obesity. VMH appears to prevent the development of insulin resistance and hypercholesterolemia which influences the energy homeostasis in male rats after high fat diet.

Vagal Hyperactivity Due to Ventromedial Hypothalamic Lesions Increases Adiponectin Production and Release

In obese humans and animals, adiponectin production and release in adipose tissue are downregulated by feedback inhibition, resulting in decreased serum adiponectin. We investigated adiponectin production and release in ventromedial hypothalamic (VMH)-lesioned animals. VMH-lesioned mice showed significant increases in food intake and body weight gain, with hyperinsulinemia and hyperleptinemia at 1 and 4 weeks after VMH-lesioning. Serum adiponectin was elevated in VMH-lesioned mice at 1 and 4 weeks, despite adipocyte hypertrophy in subcutaneous and visceral adipose tissues and increased body fat. Adiponectin production and mRNA were also increased in both adipose tissues in VMH-lesioned mice at 1 week. These results were replicated in VMH-lesioned rats at 1 week. Daily atropine administration for 5 days or subdiaphragmatic vagotomy completely reversed the body weight gain and eliminated the increased adiponectin production and release in these rats, with reversal to a normal serum adiponectin level. Parasympathetic nerve activation by carbachol infusion for 5 days in rats increased serum adiponectin, with increased adiponectin production in visceral and subcutaneous adipose tissues without changes of body weight. These results demonstrate that activation of the parasympathetic nerve by VMH lesions stimulates production of adiponectin in visceral and subcutaneous adipose tissues and adiponectin release, resulting in elevated serum adiponectin.

Effect of gender on food intake, adiposity and immunological responses following lesion of ventromedial hypothalamus in albino Wistar rats

Background and Aim: The present study was conducted to assess the gender difference in the role of ventromedial hypothalamus (VMH) on the regulation of food intake (FI), body weight (BW), and immunological responses in albino Wistar rats. Methods: A total of 24 albino Wistar rats were taken for the study and were divided equally into two groups: VMH Group and control Group for VMH lesion, with six male and six female rats in each group. In the experimental group, bilateral electrolytic lesion of the respective nuclei was performed by stereotaxy and postlesion parameters were recorded. In the control group, sham lesion was made. Male‑female difference in each parameter was determined. Results: Following VMH lesion, FI increased significantly in both the sexes (P < 0.001) but the percentage increase in FI was more in female rats. Though both male and female rats showed increase in their BW, in males the increase was significant (P < 0.001). CD4 (Cluster of differentiation 4) concentration decreased significantly in male rats (P < 0.001). Albumin levels decreased significantly (P < 0.01) in both male and female rats, following VMH lesion. Conclusion: The above‑mentioned findings suggest that VMH is an important center for satiety and adiposity in rat models and has differential influence on control of FI and BW gain in male and female rats. The impact of VMH on immunity is stimulatory and the system is more developed in males.

Relationships between ventromedial hypothalamic lesions and the expressions of neuron-related genes in visceral organs

Although the ventromedial hypothalamus (VMH) is one of the centers of parasympathetic nervous system, to date, there has been little reported regarding the role of the hypothalamus in directly changing the expression of neuron-related genes in visceral organs. Recently it has been reported that VMH lesions can directly change the expression of neuron-related genes families in visceral organs. The present review focuses on the relationships between the central nervous system, including the VMH, and the expressions of neuron-related genes in visceral organs.

Enhanced expression of nesfatin/nucleobindin-2 in white adipose tissue of ventromedial hypothalamus-lesioned rats

Nesfatin-1, an anorexigenic protein, is ubiquitously expressed in the body. However, the exact mechanism underlying the in vivo regulation of production of nesfatin/nucleobindin-2 (NUCB2), a precursor protein of nesfatin-1, is unknown. We investigated the influence of modulation of autonomic nerve activity by a ventromedial hypothalamus (VMH) lesion and the subsequent effect on nesfatin/NUCB2 production in rat tissues innervated by the peripheral nervous system. Nesfatin/NUCB2 is strongly expressed in the pancreas and liver, moderately expressed in subcutaneous and visceral fat tissues and interscapular brown adipose tissue (iBAT), but is weakly expressed in the skeletal muscles. Our study results showed that the VMH lesion in VMH-lesioned rats did not affect nesfatin/NUCB2 expression in the pancreas, liver, skeletal muscle, and iBAT; however, the protein expression was significantly high in both subcutaneous and visceral fat tissues. In addition, continuous peripheral administration of carbachol for 5 days did not affect nesfatin/NUCB2 expression, but chemical sympathectomy using 6-hydroxydopamine mimicked the effect of VMH lesion by showing significantly high nesfatin/NUCB2 expression in the subcutaneous fat tissues. These results show that VMH lesion can modulate the autonomic nervous system activity and balance and increase nesfatin/NUCB2 expression in white adipose tissues of rats. Further, this action may be mediated via inhibition of the sympathetic nerve activity.

Ventromedial hypothalamic lesions enhance small intestinal cell proliferation in mice

We have found previously that ventromedial hypothalamic lesions (VMH) enhance cell proliferation in the visceral organs through vagal hyperactivity in rats. The goal of the current study was to determine the characteristics and nature of cell proliferation in the small intestine in VMH-lesioned mice. The weight and length of the small intestine, thickness of the mucosal and muscle layers, number of proliferating cell nuclear antigen (PCNA)-positive cells, and mitotic cell count in the mucosal layer in VMH-lesioned and Sham VMH-lesioned mice were determined at 7 days after the operation. The weight and length of the small intestine in VMH-lesioned mice were significantly greater than those in Sham VMH-lesioned mice, by 11.6% and 15.0%, respectively. The thicknesses of the mucosal and muscle layers of the small intestine in VMH-lesioned mice were also significantly greater than those in Sham VMH-lesioned mice, by 12.7% and 12.5%, respectively. PCNA-positive cells and mitotic cells in the mucosal layer were densely present in crypts in VMH-lesioned mice, and were significantly increased by 31.9% and 71.7%, respectively, compared to Sham VMH-lesioned mice. These results demonstrate that VMH lesions in mice enhance cell proliferation in the mucosal layers and cause cell hypertrophy or cell proliferation in the muscle layers of the small intestine, which increases the weight and length of the small intestine. VMH lesions in mice may be a new tool for identifying growth factors and related genes involved in enlarging the small intestine mainly through cell proliferation.

Beneficial effects of ventromedial hypothalamus (VMH) lesioning on function and morphology of the liver after hepatectomy in rats

Liver has a high regenerative capacity and restores its mass and function shortly after partial hepatectomy through increased proliferation and metabolic modification of hepatocytes. The proliferation of hepatocytes can be triggered by its mass reduction after hepatectomy or by the neural factors including lesioning of the ventromedial hypothalamus (VMH). In the present study, we examined the effect of VMH lesioning on liver regeneration in hepatectomized rats by evaluating liver function and morphology. We found that functional deficits caused by partial hepatectomy [prolonged prothrombin time (PT), increased indocyanine green (ICG) retention, and decrease in PAS (periodic Acid-Schiff staining)-positive hepatocytes] were restored by VMH lesioning at 1week after the surgery, whereas these alterations disappeared at 4weeks. Morphologically, lipid microdroplets, which are considered to be important for maintaining contiguous liver function via supplying fuel for cell proliferation, were found to accumulate in hepatocytes of the hepatectomized rats at early period (1day) after partial hepatectomy. Interestingly, such lipid microdroplets were also detected in the VMH lesioned rats and the more abundantly in the VMH lesioned, hepatectomized rats up to 1week after the surgery. In conclusion, our results suggest that VMH lesioning in rats promotes recovery of liver anatomically and functionally after partial hepatectomy by promoting cell proliferation process.

Cell proliferation in visceral organs induced by ventromedial hypothalamic (VMH) lesions: Development of electrical VMH lesions in mice and resulting pathophysiological profiles

We have found that ventromedial hypothalamic (VMH) lesions produced by electrocoagulation induce cell proliferation in visceral organs through vagal hyperactivity, and also stimulate regeneration of partially resected liver in rats. To facilitate identification of proliferative and/or regenerative factors at the gene level, we developed electrical production of VMH lesions in mice, for which more genetic information is available compared to rats, and examined the pathophysiological profiles in these mice. Using ddy mice, we produced VMH lesions with reference to the previously reported method in rats. We then examined the pathophysiological profiles of the VMH-lesioned mice. Electrical VMH lesions in mice were produced using the following coordinates: 1.6 mm posterior to the bregma, anteriorly; 0.5 mm lateral to the midsagittal line, transversely; and 0.2 mm above the base of the skull, vertically, with 1 mA of current intensity and 10 s duration. The VMH-lesioned mice showed similar metabolic characteristics to those of VMH-lesioned rats, including body weight gain, increased food intake, increased percentage body fat, and elevated serum insulin and leptin. However, there were some differences in short period of hyperphagia, and in normal serum lipids compared to those of VMH-lesioned rats. The mice showed a similar cell proliferation in visceral organs, including stomach, small intestine, liver, and, exocrine and endocrine pancreas. In conclusion, procedures for development of VMH lesions in mice by electrocoagulation were developed and the VMH-lesioned mice showed pathophysiological profiles similar to those of VMH-lesioned rats, particularly in cell proliferation in visceral organs. These findings have not been observed previously in gold thioglucose-induced VMH-lesioned mice. This model may be a new tool for identifying factors involved in cell proliferation or regeneration in visceral organs.

Lasker Lauds Leptin

This year, the Albert Lasker Basic Medical Research Award will be shared by Douglas Coleman and Jeffrey Friedman for their discovery of leptin, a hormone that regulates appetite and body weight. By uncovering a critical physiologic system, their discovery markedly accelerated our capacity to apply molecular and genetic techniques to understand obesity.

Gene Expression Profiling in Rat Pancreas After Ventromedial Hypothalamic Lesioning

We previously reported that vagal hyperactivity produced by ventromedial hypothalamic (VMH) lesions stimulated cell proliferation of rat pancreatic islet B and acinar cells primarily through a cholinergic receptor mechanism. This study examined how gene families involved in cell proliferation are regulated after VMH lesions formation. Total pancreatic RNA was extracted, and differences in the gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH-lesioned rats were investigated using DNA microarray and real-time polymerase chain reaction. The VMH lesions regulated the genes that are involved in functions related to cellular growth and proliferation and neuronal development in the pancreas. Real-time polymerase chain reaction also confirmed that gene expressions of angiotensin II receptor-like 1 (AGTRL1) and proline rich 15 (PRR15) were down-regulated at day 3 after the VMH lesions. Ventromedial hypothalamic lesions may change the expression of cell proliferation-related genes and neuron-related genes in a rat pancreas.

Ventromedial and medial preoptic hypothalamic ibotenic acid lesions potentiate systemic morphine analgesia in female, but not male rats

Sex differences in systemic morphine analgesia occur with male rodents displaying significantly greater analgesic magnitudes and potencies than females. Neonatal androgenization, and to a lesser degree, adult ovariectomy enhance systemic morphine analgesia in female rats, implicating both organizational and activational effects of gonadal hormones. The neuroanatomical circuits sensitive to sex-related hormones by which females display a smaller opiate analgesic effect is not clear, but the ventromedial (VMH) and medial preoptic (MPOA) hypothalamic nuclei are critical in the monitoring of estradiol and other sex hormone levels. To assess the contribution of these nuclei to sex and adult gonadectomy differences in systemic morphine analgesia, intact male, intact female and adult ovariectomized (OVEX) female rats received bilateral saline (SAL) or ibotenic acid (IBO) microinjections into either the VMH or MPOA. Following surgeries, baseline tail-flick latencies over 120 minutes (min) were assessed over 4 days in all nine groups with intact females tested in the estrus phase of their cycle. All animals then received an ascending series of morphine (1.0, 2.5, 5.0, 7.5, 10.0 mg/kg) injections 30 min prior to the tail-flick test time course with 8–12 day inter-injection intervals between doses. Baseline latencies failed to differ between SAL-treated intact males and females, but were significantly higher in SAL-treated OVEX females. Both VMH IBO and MPOA IBO lesions increased baseline latencies in intact male and female rats, but not in OVEX females. SAL-treated intact males (ED 50 = 4.0 mg/kg) and SAL-treated OVEX females (ED 50 = 3.5 mg/kg) displayed significantly greater potencies of systemic morphine analgesia than SAL-treated intact females (ED 50 = 6.3 mg/kg), confirming previous gender and gonadectomy differences. Neither VMH IBO (ED 50 = 3.7 mg/kg) nor MPOA IBO (ED 50 = 4.1 mg/kg) males differed from SAL-treated males in the potency of systemic morphine analgesia. In contrast, VMH IBO (ED 50 = 4.1 mg/kg) and MPOA IBO (ED 50 = 3.5 mg/kg) intact females displayed significantly greater potencies in systemic morphine analgesia than SAL-treated intact females. However, VMH IBO OVEX (ED 50 = 3.5 mg/kg) and MPOA IBO OVEX (ED 50 = 3.9 mg/kg) failed to differ from SAL-treated OVEX females in the potency of systemic morphine analgesia. The magnitudes of systemic morphine analgesia as measured by Maximum Percentage Effect values displayed similar patterns, but lesser degrees, of effects. These data suggest that VMH and MPOA nuclei act to tonically inhibit endogenous pain-inhibitory circuits in the intact female, but not intact male brain, and that removal of circulating gonadal hormones by OVEX and/or excitotoxic destruction of these estrogen receptor accumulating nuclei disinhibit the female analgesic response to systemic morphine.

VMH lesions downregulate the expression of Per2 gene in the pancreas in the rat

The mammalian circadian system contains both central and peripheral oscillators. It was reported that the rhythmic expressions of period homolog 2 (per2) mRNA in peripheral tissues were abolished by the suprachiasmatic nucleus (SCN) lesions. However, there are no reports that ventromedial hypothalamic (VMH) lesions can directly affect the expression of clock genes in pancreas and liver. In the present study, we examined whether VMH lesions can affect the expression of the clock gene, per2 in these organs. Total RNA was extracted from rat pancreas and liver tissues, and differences in the gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH-lesioned rats were investigated using DNA microarray and real-time quantitative analysis. These results showed that VMH lesions downregulated the expression of the clock gene, per2 in the pancreas, but not the liver in the morning. There is a possibility that VMH lesions may affect the expression of the clock gene, per2 in the pancreas.