The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice

Abstract Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.

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Capsaicin-sensitive fibers are required for the anorexic action of systemic but not central bombesin

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.6.r1617 ◽

1999 ◽

Vol 276 (6) ◽

pp. R1617-R1622 ◽

Cited By ~ 6

Author(s):

David Michaud ◽

Hymie Anisman ◽

Zul Merali

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Neural Circuits ◽

Body Weight Gain ◽

Systemic Effects ◽

Neuronal System ◽

Afferent Neurons ◽

The Brain

Bombesin (BN) suppresses food intake in rats whether given centrally or systemically. Although the brain BN-sensitive receptors are known to be essential for the anorexic effect of systemic BN, the mode of communication between the gut and the brain remains unclear. This study assessed whether the anorexic effect of systemic BN is mediated humorally or via neural circuits. Afferent neurons were lesioned using capsaicin (50 mg/kg sc) on postnatal day 2, and responses to BN were assessed during adulthood. Capsaicin treatment decreased body weight gain significantly from postnatal age 4–7 wk. Peripheral BN (4–16 μg/kg ip) dose dependently suppressed food intake in control animals. However, this effect was completely blocked in capsaicin-treated rats. In contrast to systemic effects, feeding-suppressant effects of centrally administered BN (0.01–0.5 μg icv) were not affected by capsaicin treatment. This research suggests that peripheral BN communicates with the brain via a neuronal system(s) whose afferent arm is constituted of capsaicin-sensitive C and/or Aδ-fibers, whereas the efferent arm of this satiety- and/or anorexia-mediating circuitry is capsaicin resistant.

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Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00358.2017 ◽

2018 ◽

Vol 315 (1) ◽

pp. E29-E37 ◽

Cited By ~ 3

Author(s):

Mariana Peduti Halah ◽

Paula Beatriz Marangon ◽

Jose Antunes-Rodrigues ◽

Lucila L. K. Elias

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Food Intake ◽

White Adipose Tissue ◽

Energy Homeostasis ◽

Body Weight Gain ◽

Adult Life ◽

Male Rats ◽

Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

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Bimatoprost promotes satiety and attenuates body weight in rats fed standard or obesity-promoting diets.

10.21203/rs.3.rs-24991/v1 ◽

2020 ◽

Author(s):

Clayton Spada ◽

Chau Vu ◽

Iona Raymond ◽

Warren Tong ◽

Chia-Lin Chuang ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Gastric Emptying ◽

Food Intake ◽

Visceral Fat ◽

Body Weight Gain ◽

Metabolic Effects ◽

Sprague Dawley ◽

Hormone Levels ◽

Gut Hormone

Abstract Background Bimatoprost negatively regulates adipogenesis in vitro and likely participates in a negative feedback loop on anandamide-induced adipogenesis. Here, we investigate the broader metabolic effects of bimatoprost action in vivo in rats under both normal state and obesity-inducing conditions. Methods Male Sprague Dawley rats were a fed standard chow (SC) diet in conjunction with dermally applied bimatoprost treatment for a period of 9–10 weeks. Body weight gain, energy expenditure, food intake, and hormones associated with satiety were measured. Gastric emptying was also separately evaluated. In obesity-promoting diet studies, rats were fed a cafeteria diet (CAF) and gross weight, fat accumulation in SQ, visceral fat and liver was evaluated together with standard serum chemistry. Results Chronic bimatoprost administration attenuated weight gain in rats fed either standard or obesity-promoting diets over a 9–10 weeks. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Additionally, SQ and visceral fat mass was distinctly affected by treatment. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Conclusions These findings suggest that bimatoprost (and possibly prostamide F2α) regulates energy homeostasis through actions on dietary intake. These actions likely counteract the metabolic actions of anandamide through the endocannabinoid system potentially revealing a new pathway that could be exploited for therapeutic development.

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Oxytocin Administration Alleviates Acute but Not Chronic Leptin Resistance of Diet-Induced Obese Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20010088 ◽

2018 ◽

Vol 20 (1) ◽

pp. 88 ◽

Cited By ~ 4

Author(s):

Mehdi Labyb ◽

Chloé Chrétien ◽

Aurélie Caillon ◽

Françoise Rohner-Jeanrenaud ◽

Jordi Altirriba

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Body Weight Gain ◽

Leptin Resistance ◽

Obese Mice ◽

Short Term ◽

Continuous Administration ◽

Pre Treatment ◽

Treatment Of Obesity

Whereas leptin administration only has a negligible effect on the treatment of obesity, it has been demonstrated that its action can be improved by co-administration of leptin and one of its sensitizers. Considering that oxytocin treatment decreases body weight in obese animals and humans, we investigated the effects of oxytocin and leptin cotreatment. First, lean and diet-induced obese (DIO) mice were treated with oxytocin for 2 weeks and we measured the acute leptin response. Second, DIO mice were treated for 2 weeks with saline, oxytocin (50 μg/day), leptin (20 or 40 µg/day) or oxytocin plus leptin. Oxytocin pre-treatment restored a normal acute leptin response, decreasing food intake and body weight gain. Chronic continuous administration of oxytocin or leptin at 40 µg/day decreased body weight in the presence (leptin) or in the absence (oxytocin) of cumulative differences in food intake. Saline or leptin treatment at 20 µg/day had no impact on body weight. Oxytocin and leptin cotreatments had no additional effects compared with single treatments. These results point to the fact that chronic oxytocin treatment improves the acute, but not the chronic leptin response, suggesting that this treatment could be used to improve the short-term satiety effect of leptin.

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Effects of Consuming Sugar-Sweetened Beverages for 2 Weeks on 24-h Circulating Leptin Profiles, Ad Libitum Food Intake and Body Weight in Young Adults

Nutrients ◽

10.3390/nu12123893 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3893 ◽

Cited By ~ 1

Author(s):

Desiree M. Sigala ◽

Adrianne M. Widaman ◽

Bettina Hieronimus ◽

Marinelle V. Nunez ◽

Vivien Lee ◽

...

Keyword(s):

Young Adults ◽

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Energy Intake ◽

Body Weight Gain ◽

Energy Requirement ◽

Area Under The Curve ◽

Sugar Sweetened Beverage ◽

Ad Libitum

Sugar-sweetened beverage (sugar-SB) consumption is associated with body weight gain. We investigated whether the changes of (Δ) circulating leptin contribute to weight gain and ad libitum food intake in young adults consuming sugar-SB for two weeks. In a parallel, double-blinded, intervention study, participants (n = 131; BMI 18–35 kg/m2; 18–40 years) consumed three beverages/day containing aspartame or 25% energy requirement as glucose, fructose, high fructose corn syrup (HFCS) or sucrose (n = 23–28/group). Body weight, ad libitum food intake and 24-h leptin area under the curve (AUC) were assessed at Week 0 and at the end of Week 2. The Δbody weight was not different among groups (p = 0.092), but the increases in subjects consuming HFCS- (p = 0.0008) and glucose-SB (p = 0.018) were significant compared with Week 0. Subjects consuming sucrose- (+14%, p < 0.0015), fructose- (+9%, p = 0.015) and HFCS-SB (+8%, p = 0.017) increased energy intake during the ad libitum food intake trial compared with subjects consuming aspartame-SB (−4%, p = 0.0037, effect of SB). Fructose-SB decreased (−14 ng/mL × 24 h, p = 0.0006) and sucrose-SB increased (+25 ng/mL × 24 h, p = 0.025 vs. Week 0; p = 0.0008 vs. fructose-SB) 24-h leptin AUC. The Δad libitum food intake and Δbody weight were not influenced by circulating leptin in young adults consuming sugar-SB for 2 weeks. Studies are needed to determine the mechanisms mediating increased energy intake in subjects consuming sugar-SB.

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Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats

Life Sciences ◽

10.1016/j.lfs.2007.08.009 ◽

2007 ◽

Vol 81 (12) ◽

pp. 1024-1030 ◽

Cited By ~ 45

Author(s):

SuJean Choi ◽

Briana DiSilvio ◽

JayLynn Unangst ◽

John D. Fernstrom

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Body Weight Gain ◽

Female Rats ◽

Male And Female ◽

Male And Female Rats ◽

Chronic Infusion

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Stimulation of food intake and weight gain in mature female rats by bovine prolactin and bovine growth hormone

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.264.6.e986 ◽

1993 ◽

Vol 264 (6) ◽

pp. E986-E992 ◽

Cited By ~ 12

Author(s):

J. C. Byatt ◽

N. R. Staten ◽

W. J. Salsgiver ◽

J. G. Kostelc ◽

R. J. Collier

Keyword(s):

Growth Hormone ◽

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Body Weight Gain ◽

Mature Female ◽

Female Rats ◽

Bovine Growth Hormone ◽

Female Rat ◽

Moisture Percentage

Recombinant bovine prolactin (rbPRL) or bovine growth hormone (rbGH) was administered to mature female rats (10/treatment group) by daily subcutaneous injection for 10 days. Doses ranged from 7 to 5,000 micrograms/day (0.03-24 mg/kg body wt). Both rbPRL and rbGH increased body weight gain and food intake, but these parameters were increased at lower doses of rbPRL (7-63 micrograms/day) than rbGH (> 190 micrograms/day). Weight gain and food intake were maximally stimulated by 190 micrograms/day rbPRL, whereas maximal increased weight gain was obtained with the highest dose of rbGH (5,000 micrograms/day). Total carcass protein was increased by both hormones; however, protein as a percentage of body weight was unchanged. Similarly, neither rbPRL nor rbGH changed the percentage of carcass moisture. Percentage of body fat was increased by rbPRL but was decreased by rbGH. Weight of the gastrointestinal tract and kidneys was increased by both hormones, but increases were in proportion to body weight gain. These data confirm that ungulate prolactin is a hyperphagic agent in the female rat. In addition, they suggest that, while prolactin stimulates growth in mature female rats, this growth is probably not via a somatogenic mechanism.

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Pulmonary delivery of peptide YY for food intake suppression and reduced body weight gain in rats

Diabetes Obesity and Metabolism ◽

10.1111/j.1463-1326.2011.01363.x ◽

2011 ◽

Vol 13 (5) ◽

pp. 408-417 ◽

Cited By ~ 12

Author(s):

P. P. Nadkarni ◽

R. M. Costanzo ◽

M. Sakagami

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Peptide Yy ◽

Body Weight Gain ◽

Pulmonary Delivery ◽

Reduced Body

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Estrogens and antiestrogens: actions and interactions with fluphenazine on food intake and body weight in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.264.6.r1214 ◽

1993 ◽

Vol 264 (6) ◽

pp. R1214-R1218 ◽

Cited By ~ 4

Author(s):

J. M. Gray ◽

S. Schrock ◽

M. Bishop

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Food Intake ◽

Ethinyl Estradiol ◽

Body Weight Gain ◽

Fatty Acid Synthetase ◽

Ovariectomized Rats ◽

Synthetase Activity ◽

Concurrent Administration

Treatment of ovariectomized rats for 3 days with 2 micrograms estradiol benzoate (E2B), 6 micrograms ethinyl estradiol, or 1-2 mg of either of the antiestrogens nafoxidine or tamoxifen led to similar decreases in food intake, body weight gain, adipose tissue lipoprotein lipase activity, and hepatic fatty acid synthetase activity, despite their different effects on uterine growth and induction of progestin receptors in pituitary and adipose tissue. Longer-term (2 wk) treatment with tamoxifen resulted in similar transient changes in food intake and body weight gain, as did treatment with E2B. Daily administration of 50 micrograms fluphenazine (FLU) led to significant decreases in body weight, although there was no change in food intake. Concurrent administration of FLU with either E2B or tamoxifen led to additive effects on body weight and food intake change. None of the treatments had any effect on in vitro binding of [3H]tamoxifen to antiestrogen binding sites in pooled hypothalamic-preoptic area samples.

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