Oral administration of lactobacilli from human intestinal tract protects mice against influenza virus infection

Aims: Our study was conducted to evaluate the potent protective effects of oral administration of probiotic Lactobacillus strains against influenza virus (Flu) infection in a mouse model. Method and Results: Lyophilized Lactobacillus rhamnosus GG (LGG) and Lactobacillus gasseri TMC0356 (TMC0356) were orally administered to BALB/c mice for 19 days. The test mice were intranasally infected with Flu A/PR/8/34 (H1N1) on day 14, and any changes in clinical symptoms were monitored. After 6 days of infection, the mice were killed and pulmonary virus titres were determined. The clinical symptom scores of mice administered oral LGG and TMC0356 were significantly ameliorated, compared to those of the control mice (P < 0·01). The pulmonary virus titres of the mice fed LGG and TMC0356 were also significantly decreased compared to those of control mice (P < 0·05). Conclusions: These results indicate that oral administration of lactobacilli, such as LGG and TMC0356, might protect a host animal against Flu infection. Significance and Impact of the Study: These results demonstrate that oral administration of selected lactobacilli might protect host animals from Flu infection by interactions with gut immunity.     

Orally administered heat-killed Lactobacillus gasseri TMC0356 can upregulate cell-mediated immunity in senescence-accelerated mice

The present study was conducted to test the ability of probiotic lactobacilli to alter age-related immunosenescence in host animals. Senescence-accelerated mouse prone 1 mice were orally fed heat-killed Lactobacillus gasseri TMC0356 (TMC0356) for 4 and 8?weeks at dosages of 10?mg?day(-1) after a 16-week period of prefeeding with a standard diet. After 4 and 8?weeks of TMC0356 intervention, splenic activation of natural killer (NK) cells and mRNA expression of cytokines and other immune molecules in the lungs were analysed. After 4 and 8?weeks, splenic NK cell activities were significantly higher in the TMC0356-fed mice compared with control mice (P?相似文献   

Enhancement of immunoregulatory effects of Lactobacillus gasseri TMC0356 by heat treatment and culture medium

Aims: The aim of this study was to investigate the influence of heat treatment and culture media on the immunoregulatory effects of a probiotic strain, Lactobacillus gasseri TMC0356 (TMC0356). Methods and Results: TMC0356 cultured in deMan–Rogosa–Sharpe and same food grade (FG) media were inactivated with the heat treatment at 70 and 90°C. Viable and heat‐killed TMC0356 were tested for their ability to induce interleukin (IL)‐12 production in the murine macrophage cell line J774.1. These TMC0356 were examined for their resistance to N‐acetylmuramidase. Their morphology was observed by scanning electron microscopy. The heat‐killed TMC0356 significantly induced IL‐12 production in J774.1 cells and exhibited enhanced resistance to N‐acetylmuramidase compared with viable TMC0356. Morphological changes were observed in TMC0356 when cultured in FG medium. Cell morphology and induction of IL‐12 production in J774.1 cells were also associated. Conclusions: These results suggest that heat treatment and culture medium composition modified the immunoregulatory effects of TMC0356 to induce IL‐12 production in macrophages. Significance and Impact of the Study: These results demonstrate that probiotic immunoregulatory effects may be modified by the processing technology of cell preparation.     

Intranasally administered Lactobacillus gasseri TMC0356 protects mice from H1N1 influenza virus infection by stimulating respiratory immune responses

We conducted a study to evaluate the possibility that intranasal administration of a new probiotic strain Lactobacillus gasseri TMC0356 (TMC0356) may protect host animals from influenza virus (IFV) infection, which was indicated by enhanced respiratory immune responses in a mouse model. After 3 days of exposure to TMC0356, BALB/c mice were intranasally infected with IFVA/PR/8/34 (H1N1). Lung cells were isolated from the tested mice and evaluated for cytotoxicity against YAC-1 cells. After intranasal treatment with TMC0356, mice showed a lower morbidity and higher survival rate compared to control mice (P < 0.05). The cytotoxicity of lung cells isolated from mice after intranasal treatment against YAC-1 cells was statistically higher than that of lung cells isolated from control mice (P < 0.05). Intranasal administration of TMC0356 significantly increased mRNA expression of interleukin (IL)-1β, tumor necrosis factor, IL-10, and monocyte chemotactic protein-1 (P < 0.01). These results suggest that intranasal administration of TMC0356 may protect the host animal from IFV infection. They also indicate that TMC0356 can enhance respiratory cell-mediated immune responses of host animals characteristically with up-regulated activation of lung natural killer cells. Further studies will evaluate the possible role of the immune stimulatory effects of TMC0356 within the protective effects of this bacterium against IFV, as observed in the present study.     

Potent effects of,and mechanisms for,modification of crosstalk between macrophages and adipocytes by lactobacilli

The murine macrophage‐like cell line J774.1 was treated with heat‐killed cells of Lactobacillus GG (LGG) and L. gasseri TMC0356 (TMC 0356). Interleukin (IL)‐6, IL‐12, and tumor necrosis factor‐α were profiled from the J774.1 cells using enzyme‐linked immunosorbent assay methods. The conditioned medium from cultured J774.1 cells was transferred to the preadipocyte cell line 3T3‐L1 (which is a mouse embryonic fibroblast‐adipose‐like cell line). Growth and differentiation of 3T3‐L1 cells were monitored by analyzing lipid accumulation and expression of peroxisome proliferator‐activated receptor (PPAR)‐γ mRNA. The medium conditioned by 3T3‐L1 cells was added to J774.1 cells and the cytokines in the supernatant analyzed. Compared with that of cells exposed to a PBS‐conditioned medium, lipid accumulation in 3T3‐L1 cells was significantly suppressed in a dose‐dependent manner by each medium that had been conditioned with LGG and TMC0356. PPAR‐γ mRNA expression in 3T3‐L1 cells was also significantly downregulated (P < 0.01, P < 0.05, respectively). The conditioned medium of 3T3‐L1 adipose phenotype significantly stimulated production of IL‐6 and IL‐12 in J774.1 cells treated with LGG and TMC0356. These results suggest that lactobacilli may suppress differentiation of preadipocytes through macrophage activation and alter the immune responses of macrophages to adipose cells.     

Lactobacillus strains stabilize intestinal microbiota in Japanese cedar pollinosis patients

A randomized double-blind, placebo-controlled trial was conducted to ascertain the intestinal microbiota-altering properties of LGG and L. gasseri TMC0356 (TMC0356) in Japanese cedar Cryptomeria japonica pollinosis patients. Fecal bacteria communities were examined before and after fermented milk administration using culture, FISH and T-RFLP methods. Test group subjects showed the presence of LGG and TMC0356 along with a significant increase in fecal lactobacilli ( P < 0.001) after giving LGG and TMC0356 fermented milk. Culture and FISH analysis revealed no significant changes in other intestinal bacterial groups. Each subject exhibited a characteristic T-RFLP profile pattern that varied quantitatively and qualitatively with JCP shedding. Profile changes were observed in 53% of placebo group subjects and in 21% of test group subject's post-administration, indicating that LGG and TMC0356 suppressed intestinal microbiota changes in JCPsis patients. The results suggest that intestinal microbiota might be more sensitive to exposure to environmental allergens than expected from the results of general culture method studies. Stabilization of intestinal microbiota by selected probiotic strains such as LGG and TMC0356 could be beneficial to homeostasis of the intestinal microbiota and useful in the management of JCPsis.     

Beneficial effect of oral administration of Lactobacillus casei strain Shirota on insulin resistance in diet-induced obesity mice

Aims: This study aimed at determining whether oral administration of a probiotic strain, Lactobacillus casei strain Shirota (LcS), can improve insulin resistance, which is the underlying cause of obesity‐associated metabolic abnormalities, in diet‐induced obesity (DIO) mice. Methods and Results: DIO mice were fed a high‐fat diet without or with 0·05% LcS for 4 weeks and then subjected to an insulin tolerance test (ITT) or oral glucose tolerance test (OGTT). Oral administration of LcS not only accelerated the reduction in plasma glucose levels during the ITT, but also reduced the elevation of plasma glucose levels during the OGTT. In addition, plasma levels of lipopolysaccharide‐binding protein (LBP), which is a marker of endotoxaemia, were augmented in the murine models of obese DIO, ob/ob, db/db and KK‐A^y and compared to those of lean mice. LcS treatment suppressed the elevation of plasma LBP levels in DIO mice, but did not affect intra‐abdominal fat weight. Conclusions: LcS improves insulin resistance and glucose intolerance in DIO mice. The reduction in endotoxaemia, but not intra‐abdominal fat, may contribute to the beneficial effects of LcS. Significance and Impact of the Study: This study suggests that LcS has the potential to prevent obesity‐associated metabolic abnormalities by improving insulin resistance.     

Heat-killed Lactobacillus gasseri TMC0356 protects mice against influenza virus infection by stimulating gut and respiratory immune responses

This study investigated whether heat-killed Lactobacillus protects host animal against influenza virus infection and stimulates their immunity. Heat-killed Lactobacillus gasseri TMC0356 was orally administered to BALB/c mice for 19 days; the mice were intranasally infected with Flu A/PR/8/34 (H1N1) on day 14, and clinical symptoms were monitored. After 6 days, the mice were sacrificed, and pulmonary virus titres were determined. Splenic activation of natural killer (NK) cells and the mRNA expression of cytokines and other immune molecules in the lung and Peyer's patch (PP) were analysed. Clinical symptom scores of mice orally fed TMC0356 ameliorated significantly (P < 0.01); their pulmonary virus titres decreased significantly compared with those of control mice (P < 0.05); their mRNA expression of interleukin (IL)-12, IL-15 and IL-21 in PP and the pulmonary mRNA expression of IFN-γ, TNF, IL-12a, IL-12rbl, IL-2rb and perforin 1 increased significantly (P < 0.05). Oral administration of heat-killed lactobacilli may protect against influenza virus infection by stimulating local and systemic immune responses. Cellular components of lactobacilli may be pivotal in protecting against viral infection by enhancing gut and respiratory immune responses.     

Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet‐induced obesity

Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high‐fat diet‐induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil‐ and macrophage‐based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi‐infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high‐fat diet, toll‐like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow‐derived macrophages from obese, B. burgdorferi‐infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice.     

Meal Pattern Analysis of Diet‐Induced Obesity in Susceptible and Resistant Rats

Objective: To characterize the meal patterns of free feeding Sprague‐Dawley rats that become obese or resist obesity when chronically fed a high‐fat diet. Research Methods and Procedures: Male Sprague‐Dawley rats (N = 120) were weaned onto a high‐fat diet, and body weight was monitored for 19 weeks. Rats from the upper [diet‐induced obese (DIO)] and lower [diet‐resistant (DR)] deciles for body‐weight gain were selected for study. A cohort of chow‐fed (CF) rats weight‐matched to the DR group was also studied. Food intake was continuously monitored for 7 consecutive days using a BioDAQ food intake monitoring system. Results: DIO rats were obese, hyperphagic, hyperleptinemic, hyperinsulinemic, hyperglycemic, and hypertriglyceridemic relative to the DR and CF rats. The hyperphagia of DIOs was caused by an increase in meal size, not number. CF rats ate more calories than DR rats; however, this was because of an increase in meal number, not size. When expressed as a function of lean mass, CF and DR rats consumed the same amount of calories. The intermeal intervals of DIO and DR rats were similar; both were longer than CF rats. The nocturnal satiety ratio of DIO rats was significantly lower than DR and CF rats. The proportion of calories eaten during the nocturnal period did not differ among groups. Discussion: The hyperphagia of a Sprague‐Dawley rat model of chronic diet‐induced obesity is caused by an increase in meal size, not number. These results are an important step toward understanding the mechanisms underlying differences in feeding behavior of DIO and DR rats.     

Bifidobacterium CECT 7765 improves metabolic and immunological alterations associated with obesity in high‐fat diet‐fed mice

Objectives: To evaluate the effects of administration of Bifidobacterium pseudocatenulatum CECT 7765 on metabolic and immune alterations in obese mice. Design and Methods: Adult male wild‐type C57BL‐6 mice were fed a standard diet or high‐fat diet (HFD), supplemented or not with B. pseudocatenulatum CECT 7765 for 7 weeks. The assessments included biochemical and immunological parameters, insulin resistance, glucose tolerance, histology of liver, white‐adipose and intestinal tissues, immunocompetent cell functions, and microbiota‐related features. Results: B. pseudocatenulatum CECT 7765 reduced serum cholesterol, triglyceride, and glucose levels and decreased insulin resistance and improved glucose tolerance in obese mice. This strain reduced serum levels of leptin, interleukin (IL)‐6 and monocyte chemotactic protein‐1, while increased those of IL‐4 in HFD‐fed mice. B. pseudocatenulatum CECT7765 reduced liver steatosis and the number of larger adipocytes and number of fat micelles in enterocytes of obese mice. The strain also improved the function of macrophages and dendritic cells in relation to phagocytosis, cytokine production, and induction of T‐lymphocyte proliferation. The strain administration increased bifidobacteria and reduced enterobacteria and the inflammatory properties of the gut content in HFD‐fed mice. Conclusion: B. pseudocatenulatum CECT 7765 was shown to ameliorate both metabolic and immunological dysfunctions related to obesity in HFD‐fed mice.     

Defective Dietary Induction of Uncoupling Protein 3 in Skeletal Muscle of Obesity‐Prone Rats

Objective: The goal of this study was to determine whether differential induction of skeletal muscle uncoupling protein 3 (UCP3) contributes to the development of diet‐induced obesity (DIO) or resistance to the development of obesity (DR) when rats are placed on a moderate fat (31%) high energy (HE) diet. Research Methods and Procedures: Gastrocnemius muscle was obtained from Sprague‐Dawley rats that were identified as DIO‐prone (n = 5) or DR (n = 5) on the basis of urinary norepinephrine excretion while consuming a chow diet. Muscle was also obtained from animals in the top tertile of weight gain (DIO_HE, n = 5) and the bottom tertile of weight gain (DR_HE, n = 5) after 2 weeks on the HE diet. UCP3 and actin mRNA levels were measured in all muscle samples by Northern analysis. To distinguish the effect of dietary energy content from the effect of obesity itself, we studied additional DIO and DR animals that had been returned to a chow diet for 10 weeks after consuming a HE diet for 10 weeks. Results: The muscle UCP3/actin mRNA ratio in animals that resisted the development of obesity during 2 weeks on the HE diet was 3‐fold higher than in the other groups (DR_HE = 3.24 ± 0.83, DIO_HE = 0.91 ± 0.20, DIO‐prone = 0.72 ± 0.15, DR = 0.63 ± 0.15; p = 0.002). However, there was no difference in muscle UCP3/actin mRNA ratios between DIO animals and DR animals that had been fed the HE diet for 10 weeks and then returned to either an ad libitum chow diet for 10 weeks (DIO = 13.8 ± 3.53, DR = 11.1 ± 3.43, p = NS) or to a restricted chow diet for 10 weeks (DIO = 11.0 ± 2.85, DR = 10.6 ± 2.20, p = NS) despite significantly greater body weight of the DIO animals. Discussion: DR animals may initially resist weight gain when placed on a HE diet through a greater induction of muscle UCP3. This induction is transient and is related more closely to dietary fat content than to body fat stores. DIO animals show no initial induction of muscle UCP3, which may contribute to their increased metabolic efficiency soon after exposure to a HE diet.     

Effect of weight loss and exercise on angiogenic factors in the circulation and in adipose tissue in obese subjects

Background:

Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF‐A), angiopoietin (ANG‐1), ANG‐2 and angiopoietin‐like protein‐4 (ANGPTL‐4).

Methods:

In this study, the independent and combined effects of diet‐induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors were investigated. Seventy‐nine obese males and females were randomized to: 1. Exercise‐only (EXO; 12‐weeks exercise without diet‐restriction), 2. Hypocaloric diet (DIO; 8‐weeks very low energy diet (VLED) + 4‐weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8‐weeks VLED + 4‐weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention.

Results:

Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF‐A protein was non‐significantly reduced in the weight loss groups. ANG‐1 protein levels were significantly reduced 22‐25% after all three interventions (P < 0.01). The ANG‐1/ANG‐2 ratio was also decreased in all three groups (P < 0.05) by 27‐38%. ANGPTL‐4 was increased in the EXO group (15%, P < 0.05) and 9% (P < 0.05) in the DIO group. VEGF‐A, ANG‐1, and ANGPTL‐4 were all expressed in human AT, but only ANGPTL‐4 was influenced by the interventions.

Conclusions:

Our data show that serum VEGF‐A, ANG‐1, ANG‐2, and ANGPTL‐4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation.     

Effects of Pravastatin on Obesity,Diabetes, and Adiponectin in Diet‐induced Obese Mice

Objective: The aim of this study was to investigate the in vivo effects of pravastatin on the development of obesity and diabetes in diet‐induced obese (DIO) mice. Methods and Procedures: We examined food intake, body‐weight changes, visceral white adipose tissue (WAT) adiponectin and resistin levels, and energy metabolism. Results: Treatment with 100 mg/kg/day pravastatin for 28 days decreased diet‐induced weight gain and visceral adiposity. In addition, the weight of the WAT, the triglyceride (TG) contents of the liver and muscles, and the levels of serum insulin improved in the pravastatin‐treated DIO mice. Furthermore, pravastatin treatment changed the WAT adiponectin and resistin mRNA expression and serum levels compared with the controls. Finally, pravastatin treatment increased oxygen consumption and decreased the respiratory quotient (RQ). Discussion: Pravastatin treatment prevents the development of obesity and diabetes in DIO mice. The prevention of obesity may be mediated by increased oxygen consumption and a decrease in the RQ. These results provide novel insights into the use of pravastatin as a therapeutic tool for metabolic syndromes.     

A dairy‐based high calcium diet improves glucose homeostasis and reduces steatosis in the context of preexisting obesity

Objective:

High dietary calcium (Ca) in the context of a dairy food matrix has been shown to reduce obesity development and associated inflammation in diet‐induced obese (DIO) rodents. The influence of Ca and dairy on these phenotypes in the context of preexisting obesity is not known. Furthermore, interpretations have been confounded historically by differences in body weight gain among DIO animals fed dairy‐based protein or high Ca.

Design and Methods:

Adiposity along with associated metabolic and inflammatory outcomes were measured in DIO mice previously fattened for 12 week on a soy protein‐based obesogenic high fat diet (45% energy, 0.5% adequate Ca), then fed one of three high fat diets (n = 29‐30/group) for an additional 8 week: control (same as lead‐in diet), high‐Ca (1.5% Ca), or high‐Ca + nonfat dry milk (NFDM).

Results and Conclusion:

Mice fed high‐Ca + NFDM had modestly, but significantly, attenuated weight gain compared to mice fed high‐Ca or versus controls (P < 0.001), whereas mice fed high‐Ca alone had increased weight gain compared to controls (P < 0.001). Total measured adipose depot weights between groups were similar, as were white adipose tissue inflammation and macrophage infiltration markers (e.g. TNFα, IL‐6, CD68 mRNAs). Mice fed high‐Ca + NFDM had significantly improved glucose tolerance following a glucose tolerance test, and markedly lower liver triglycerides compared to high‐Ca and control groups. Improved metabolic phenotypes in prefattened DIO mice following provision of a diet enriched with dairy‐based protein and carbohydrates appeared to be driven by non‐Ca components of dairy and were observed despite minimal differences in body weight or adiposity.     

Preproghrelin-derived peptide, obestatin, fails to influence food intake in lean or obese rodents

Objectives: Obestatin has been initially characterized as a new peptide derived from the ghrelin precursor, which suppresses food intake and inhibits the orexigenic and prokinetic actions of ghrelin when injected peripherally or centrally in lean mice. However, reproducing these data remains controversial. Reasons for the disparity may be the use of different doses, routes, and animal models. We aimed to investigate the effects of peripheral and intracisternal (IC) injection of obestatin on feeding, gastric motility, and blood glucose in rats as well as in diet‐induced obese (DIO) mice. Research Methods and Procedures: Food intake and gastric emptying of a semi‐liquid caloric meal were measured after intraperitoneal (IP) injection of obestatin in rats and DIO mice. Gastric phasic motility and blood glucose were monitored in urethane‐anesthetized rats after IC or intravenous (IV) injection of obestatin. Results: Obestatin injected intraperitoneally at doses ranging from 0.1 to 3 mg/kg influenced neither acute food intake nor gastric emptying in rats. Obestatin injected intravenously at 0.3 or 3 mg/kg and IC at 7.5 or 30 µg/rat modified neither fasted gastric phasic motility nor blood glucose levels, while ghrelin (30 µg/kg, IV) increased and vagotomy suppressed gastric motility, and an oligosomatostatin analog (3 µg/rat, IC) decreased blood glucose. Obestatin, injected intraperitoneally (0.3 mg/kg) in DIO mice, did not alter feeding response to a fast, while urocortin 1 (10 µg/kg, IP) induced a 73.3% inhibition at 2 hours. Discussion: Our data demonstrate that peripheral administration of obestatin did not modify food intake in rats or obese mice or gastric motor function in rats.     

Adipose tissue‐specific modulation of galectin expression in lean and obese mice: Evidence for regulatory function

Objective:

Galectins (Gal) exert many activities, including regulation of inflammation and adipogenesis. We evaluated modulation of Gal‐1, ‐3, ‐9 and ‐12 in visceral (VAT) and subcutaneous (SAT) adipose tissue in mice.

Design and Methods:

We used two mouse models of obesity, high‐fat diet induced obesity (DIO) and ob/ob mice. We also evaluated the response of Gal‐1 KO mice to DIO.

Results:

Both age and diet modulated expression of galectins, with DIO mice having higher serum Gal‐1 and Gal‐3 versus lean mice after 13‐17 weeks of high‐fat diet. In DIO mice there was a progressive increase in expression of Gal‐1 and Gal‐9 in SAT, whereas Gal‐3 increased in both VAT and SAT. Expression of Gal‐12 declined over time in VAT of DIO mice, similar to adiponectin. Obesity lead to increased production of Gal‐1 in adipocytes, whereas the increased Gal‐3 and Gal‐9 of obesity mostly derived from the stromovascular fraction. Expression of Gal‐12 was restricted to adipocytes. There was increased production of Gal‐3 and Gal‐9, but not Gal‐1, in CD11c^? and CD11c⁺ macrophages from VAT of DIO versus lean mice. Expression of Gal‐1, ‐3 and ‐12 in VAT and SAT of ob/ob mice followed a trend comparable to DIO mice. Rosiglitazone reduced serum Gal‐1, but not Gal‐3 and modulated expression of Gal‐3 in VAT and Gal‐9 and Gal‐12 in SAT of DIO mice. High‐fat feeding lead to increased adiposity in Gal‐1 KO versus WT mice, with loss of correlation between leptin and adiposity and no alterations in glucose and insulin levels.

Conclusions:

Obesity leads to differential modulation of Gal‐1, 3, 9 and 12 in VAT and SAT, with Gal‐1 acting as a modulator of adiposity.

     

Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol

Objective

Acute administration of cannabinoid CB₁ receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice.

Methods

Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally.

Results

THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice.

Conclusions

Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity.