Weight and Glucose Control in Rats Submitted to Sleeve Gastrectomy with Cafeteria Diet-Induced Obesity

Abstract

Introduction:

Sleeve gastrectomy (SG) has been widely disseminated as a surgical treatment for obesity and associated comorbidities, and currently it is one of the most performed surgeries in the world. Experimental research is becoming increasingly relevant to characterize the pathophysiological mechanisms induced by it.

Objective:

The aim of this study was to standardize an experimental model of SG in rats with obesity induced using a cafeteria diet (CAF) and evaluate variations in weight and glycemic control after vertical SG, maintaining the CAF.

Materials and Methods:

Twenty Rattus norvegicus albinus rats, Wistar strain, with an average weight of 250 g were used. The animals were randomized into two groups and underwent 4 weeks of obesity induction before the procedure. In 10 animals of the SG group, vertical SG was performed, and in 10 animals of the control/sham (C) group, simulated surgery was performed, consisting of laparotomy and bidigital compression of the stomach. The animals were followed for a total of 8 weeks, with the weight assessed weekly and fasting blood glucose assessed before the start of the CAF, at the time of surgery, and after 4 weeks of the postoperative period, when they were sacrificed.

Results:

Before obesity induction, the average weight was 257.8 g in the SG group 266.1 g in the C group. After obesity induction, the average weight was 384 g in the vertical sleeve gastrectomy group and 374.8 g in the C group. In the fourth postoperative week, the average weight was 391.6 g in the VSG group and 436.6 g in the C group. The average blood glucose levels were 88.7, 101.8, and 91.3 mg/dL in the VSG group and 86.6, 103.1, and 109.4 mg/dL in the C group, respectively, before the start of the diet, in the fourth preoperative week, and in the fourth postoperative week.

Conclusions:

Vertical SG in rats is feasible and promotes glycemic control in the postoperative period. CAF allows induction of obesity and changes in blood glucose.

Introduction

Obesity has become a global epidemic with high rates of morbidity and mortality due to its association with conditions such as type 2 diabetes mellitus (DM2).¹ The relationship between obesity and diabetes is constant as obesity often leads to development of metabolic syndrome, characterized by a set of metabolic and hormonal alterations such as systemic arterial hypertension, elevated blood glucose, dyslipidemia, and abdominal obesity. Its persistence usually leads to development of DM2.² It is observed that about 90% of patients with DM2 are either obese or overweight. Bariatric surgery is a therapeutic option for obesity, improving its clinical consequences and controlling comorbidities.³

According to current guidelines, bariatric surgery is considered for obese patients with a body mass index (BMI) ≥40 kg/m² or those with a BMI between 35 and 40 kg/m² and who have comorbidities. Therefore, there are a large number of obese diabetic patients who are candidates for the surgical procedure.⁴ More recently, the Brazilian Society of Bariatric and Metabolic Surgery (SBCBM) issued an opinion by consensus, in which bariatric surgery could be indicated for diabetic patients with a BMI between 30 and 34.9 kg/m² due to the proven effectiveness of the procedure as a metabolic surgery and in controlling DM2.⁵

Diabetes mellitus (DM) is defined as a group of metabolic disorders characterized by chronic hyperglycemia regardless of its etiology. The main reported complications are diabetic retinopathy, chronic kidney disease, cardiovascular diseases, increased susceptibility to infections, diabetic neuropathy, and delayed wound healing.⁶

In 2010, its global prevalence was estimated at 6.4% of the adult population (20–70 years old), with a projected increase to 7.7% by 2030.⁷ Currently, ∼422 million people worldwide are affected by DM2, accounting for 5.2% of deaths (the fifth leading cause of death).⁸ About 90% of individuals with DM2 are overweight or obese.⁹ Twenty-three percent of people with morbid obesity have DM2, and only 8% are diagnosed. The total cost of diabetes was estimated to be at least US$ 245 billion in 2013, with US$ 176 billion in direct costs and US$ 69 billion in productivity loss, in the United States.¹⁰

Currently, DM2 is considered a high-impact endemic disease in developing countries, where about two-thirds of diagnosed individuals live. The World Health Organization (WHO) classifies it as one of the four priority noncommunicable diseases.⁸ In Brazil, the epidemiological behavior of the disease in recent decades has been characterized by an exponential increase in incidence—due to the growing elderly population, prevalence of obesity, and sedentary lifestyle—equivalent to the challenge posed by infectious diseases.⁶

According to the Brazilian Diabetes Society—SBD, there are currently 12,054,827 diabetic individuals in the country.¹¹ According to the Department of Informatics of the Unified Health System (SUS) of Brazil, in the public sector, 1,036,007 people were diagnosed between January 2008 and April 2015, with higher incidence in the southeast region (35% of cases), followed by the northeast region (31% of cases); and in the state of São Paulo, 164,010 cases were diagnosed during the same period.¹²

Sleeve gastrectomy (SG) has been widely disseminated as a surgical treatment for obesity and associated comorbidities such as DM2 and is currently one of the most performed surgeries in the world for this purpose.¹³ The results regarding excess weight loss and consequent reduction of BMI and treatment of diseases related to this condition are supported by various studies.^14,15

Thus, experimental research aimed at demonstrating the effectiveness and mechanisms related to the results of SG plays a fundamental role in elucidating its mechanims of weigh loss induction.

In the literature, various models for inducing obesity and diabetes in rats through diet can be found.^16–18 There are also several protocols for performing SG in these animals, making it possible to replicate the surgical procedure.^19,20 However, these models do not mimic situations that can lead to weight regain after SG, such as maintenance of high-calorie liquid intake in the diet.

In this context, vertical gastrectomy is already recognized as an effective method in controlling excess weight and, consequently, associated comorbidities such as DM2.²¹ However, the metabolic mechanism of vertical gastrectomy is not yet fully understood and there are several hypotheses to explain it.

Rat models such as Goto–Kakizaki, which have genetically induced DM2, support the metabolic role of SG independent of weight loss. It has been demonstrated that vertical gastrectomy reduces glycosylated hemoglobin and improves glycemic control.²² Another important piece of evidence is demonstration of improved glucose tolerance with a decrease in ghrelin.²³

Additionally, another aspect of great relevance is the increase in glucagon-like peptide 1 (GLP1) after vertical gastrectomy. It has also been demonstrated that there is an increase in GLP1 independent of weight loss.²⁴ This increase can be attributed to a decrease in gastric emptying time, with GLP1 being one of the determinants for the metabolic benefits after SG.^24,25

Therefore, the study of weight and glycemic control after SG is of utmost importance to standardize an experimental model for evaluating the metabolic role of SG and the association between weight variables and glycemic control. Consequently, conducting an experimental study with this operation in rats can contribute to a better understanding of its pathophysiology.^26,27

Materials and Methods

This experimental study is part of the research line “Study of morphofunctional changes in vertical gastrectomy in rats with diet-induced cafeteria obesity” conducted by the Research Group on Morphofunctional Changes in Obesity at the Federal University of Maranhão, Brazil. The study was carried out at the Experimental Surgery Laboratory of the Federal University of Maranhão, following approval from the Ethics Committee for Animal Use of both the Federal University of Maranhão (Process No. 23115.003386/2020–09) and University of São Paulo (Process No. 1390/2020).

The principles of animal experimentation according to applicable legislation (Law 11.794 and Resolutions of the National Council for the Control of Animal Experimentation—CONCEA/BRAZIL, 2008) were followed.

Sample

The sample consisted of 20 adult male rats of the Rattus norvegicus albinus species, Wistar lineage, with an average body weight of 250 g, which were obtained from the Animal Facility of the Federal University of Maranhão. The number of animals in the sample was determined using the Experimental Design Assistant computer program available on the NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research) website, through power analysis with two tails and an effect size |ρ| of 0.5, probability of error of 0.05, and power of 0.95 (1-β probability of error).

This resulted in a total of 20 animals, aiming to use the smallest number of animals possible to achieve statistical significance for the studied variables. Throughout the experiment, the animals were kept under controlled noise and temperature conditions (23°C ± 1°C), with a 12-hour light–12-hour dark cycle, and hygiene conditions were maintained by changing the Xilana^® used as bedding for the cages, as needed.

The animals underwent a 7-day adaptation period during which they received standard Purilab^® feed and filtered water ad libitum. Afterward, they were introduced to a hypercaloric cafeteria diet (CAF), which was maintained from the beginning of the fattening phase until euthanasia of the animals in the final experimental stage, except for the 8 hours preceding the surgical procedures when the animals were fasted and in the immediate postoperative period (first 24 hours) when the animals received only liquids and no solid diet.

The animals were randomized and grouped into groups of five and housed in polypropylene drawer-type cages measuring 40 × 35 × 15 cm and lined with 2 cm of Xilana. Cages were numbered and placed on horizontal shelves designated for this purpose. Each animal in each cage was identified by color markings on its tail.

The experiment was conducted in the experimental surgical center of the Experimental Surgery Laboratory of the Federal University of Maranhão. After the adaptation period, the animals were weighed and randomly assigned to compose the two study groups, and induction of obesity began through a hypercaloric CAF.

Induction of obesity

The standard diet used was Purilab rat feed. According to the manufacturer, 100 g of this diet contains 23% proteins, 49% carbohydrates, 4% total lipids, 5% fiber, 7% ash, and 6% vitamins, totaling 4.07 kcal/g.

To induce obesity in the animals, a CAF was used,^16,17 so named because it contains hypercaloric foods. It consisted of a solid part, which was associated with the standard feed, prepared manually by mixing crushed food, including 500 g of bacon, 1 kg of roasted peanuts, 1 kg of cornstarch biscuits, and 500 g of milk chocolate. The liquid part of the diet included filtered water and soda, a hypercaloric liquid.

This protocol for inducing obesity was adapted by the Experimental Surgery Laboratory of the Federal University of Maranhão, aiming to introduce a liquid component to the diet.²⁸ The hypercaloric diet protocol was analyzed by the Physiology Laboratory of the Federal University of Maranhão, determining that this mixture contains 506.2 kcal/100 g, with a nutritional value consisting of 35.3% carbohydrates, 34.5% lipids, and 15.4% proteins.

All foods, both the standard feed and CAF, were offered ad libitum to the animals throughout the 8-week experiment, including 4 weeks of obesity induction and 4 weeks of postoperative follow-up. The weight of the animals was measured weekly during the experiment, using a Plenna digital electronic precision scale, and rats were considered obese if their weight increased by 30% after the start of the hypercaloric diet.

Study design

Groups

All animals underwent surgical treatment performed by the same researcher and assistant. The obesity induction period lasted for 4 weeks, equivalent to 28 days, and the postoperative follow-up period also lasted for 4 weeks, after which euthanasia was performed.

The rats were randomized and divided into two groups: the control/sham group (C) with 10 animals and SG with 10 animals. In the animals of the C group, a simulated operation was performed using bidigital manipulation of the stomach, while in the SG, the SG procedure was carried out.

Anesthesia and antibiotic prophylaxis

The animals were fasted for 8 hours before the surgical procedure, which was performed under anesthesia, using a combination of 10% ketamine hydrochloride at a dose of 100 mg/kg and 2% xylazine hydrochloride at a dose of 10 mg/kg, administered intraperitoneally with an insulin syringe and needle after manual restraint of the animal.

The anesthetic depth was assessed throughout the surgical procedure by evaluating the ocular reflex,²⁹ ensuring that the animals remained anesthetized throughout the entire surgical procedure. If necessary, additional anesthesia was provided with one-third of the initial anesthetic combination. Immediately after anesthetic induction and before the start of the surgical procedure, antibiotic prophylaxis was performed with intramuscular ceftriaxone at a dose of 50 mg/kg.

Surgical procedures

Procedures common to both groups

After anesthetic induction, the animals were placed in the dorsal recumbent position on a wooden board measuring 15 by 15 cm and secured with adhesive tape. The abdominal area was then epilated, and the operative site was aseptically prepared using a 10% povidone–iodine alcoholic solution. A sterile, fenestrated surgical drape was placed over the animal.

Access to the abdominal cavity was achieved through a median laparotomy, with dissection performed in layers until the peritoneal cavity was opened, ∼5 cm from the xiphoid process, along the midline of the abdomen, using a disposable cold scalpel with a number 15 blade.

Control/sham group

In the 10 animals of the C group, after accessing the abdominal cavity, an orogastric cannulation was performed using a size eight Nelaton^® catheter and the stomach was identified. A bidigital manipulation of the ventral and dorsal walls of the gastric body was then performed. Subsequently, the abdominal wall was closed with continuous sutures using 4.0 Vicryl Ethicon^® polyglactin thread, and the skin was closed with intradermal continuous sutures using 4.0 Vicryl Ethicon polyglactin thread.

Vertical gastrectomy group

In the 10 animals of the vertical gastrectomy group, after accessing the abdominal cavity, an orogastric cannulation was performed using a size eight Nelaton catheter, and the stomach was identified and calibrated with the diameter of this catheter. Two anatomical reference points were used, with one proximal point located at the esophagogastric junction of the gastric fundus and another distal point located 15 mm from the pylorus.

The gastric excision plane was marked using a Crile-type hemostatic clamp, and then dissection and resection of the gastric fundus, part of the body, and antrum on the greater curvature of the stomach were performed, followed by closure of the dissection line with continuous extramucosal sutures using 5.0 Vicryl Ethicon polyglactin thread.

Subsequently, the abdominal wall was closed with continuous sutures using 4.0 Vicryl Ethicon polyglactin thread, and the skin was closed with intradermal continuous sutures using 4.0 Vicryl Ethicon polyglactin thread.

Postoperative care

During the anesthetic recovery process, the animals were kept warm using a red incandescent lamp to avoid stress and then they were returned to their respective cages after complete anesthesia recovery. They were maintained under the same conditions of care and hygiene as described above.

In the immediate postoperative period (first 24 hours), the animals remained fasting from solid food, but had access to water with glucose (two vials of 50% glucose in 500 mL of water) ad libitum. From the first day after surgery, a full diet was reintroduced, including standard feed, filtered water, and solid and liquid CAF.

Postoperative analgesia was provided during the first 72 hours after the procedure, using oral paracetamol at a dose of one drop (10 mg) per 25 mL of water, following the protocol of the Experimental Surgery Laboratory of the Federal University of Maranhão.

Euthanasia and disposal of biological material

Euthanasia was performed at the end of the eighth week of the experiment, after data collection and measurements of study variables, in a quiet environment by a trained team, individually and isolated from other animals, using an anesthetic overdose. The overdose was three times the anesthetic dosage of 10% ketamine hydrochloride at a dose of 100 mg/kg and 2% xylazine hydrochloride at a dose of 10 mg/kg, which was administered intraperitoneally.

Confirmation of animal death was based on the observation of signs of apnea, asystole, paleness of mucous membranes, and absence of corneal reflex. The carcasses were placed in white plastic bags, properly identified, and frozen in a freezer until they were delivered to the Central Animal Facility of the Federal University of Maranhão for subsequent incineration by the biological waste selective collection company of the unit.

Study variables

Body weight

All animals were weighed weekly throughout the study period, that is, at the time of randomization and the start of obesity induction through the CAF and at all subsequent weeks until euthanasia. Body weight was measured using a Plenna digital electronic precision scale and recorded in the standardized data collection form for each animal.

Fasting glycemia

Capillary fasting glycemia was determined by measures of fasting glucose levels after 8 hours of fasting, using an Active Accu-Chek^® glucometer, and recorded in the standardized data collection form for each animal. Fasting glycemia was measured before starting the hypercaloric diet, before anesthetic induction on the day of surgery, and 4 weeks after the procedure.

Statistical analysis

Data were analyzed using the Jamovi 2021 software. To assess the effect on the dependent variables, weight and fasting glycemia, in the two groups and the studied weeks, the Shapiro–Wilk normality test was initially performed. As all measurements showed a normal distribution (P > .05), Student's t-test was applied to compare quantitative variables in the two independent groups. The level of significance to reject the null hypothesis was set at 5%, meaning a value of P < .05 was considered statistically significant.

Results

The experimental stages proceeded according to the study design without any impediments to experiment execution. The surgical procedures occurred as planned, and there were no animal deaths, sample loss, complications, or postoperative complications until the moment of euthanasia. The anesthetic plan for the surgical procedure and the postanesthetic recovery were adequate in all animals.

Body weight changes during the obesity induction period

The average weight of the animals before the start of the obesity induction period was 266.1 g in the C group and 257.8 g (P = .240) in the vertical gastrectomy group. After 4 weeks/28 days of feeding with the hypercaloric CAF, the animals reached an average weight of 383.9 and 384 g (P = .993), representing a weight gain of 38.73% and 48.95%, respectively, compared with the initial weight in the C and vertical gastrectomy groups.

Thus, all animals were considered obese after the induction period and were eligible for the study. The weekly weight gain was equivalent in all groups, with no statistical difference in the intergroup comparison according to Student's t-test (Table 1). The evolution of the average body weight of each group during the obesity induction period is shown in Figure 1.

FIG. 1.

Boxplot 1: Preoperative weight (median and IQR), sham group.

Table 1.

Weight Induction

Assessment time points	SG	SD	Control	SD	P
First week	257.8	± 19	266.1	± 10.3	.240
Fourth postdiet week	384	± 24.7	383.9	± 28	.993
First postoperative week	358.7	± 25.3	395.1	± 26.7	.006
Fourth postoperative week	391.6	± 29.9	436.6	± 32.2	.001

Control, control/sham group; SD, standard deviation; SG, sleeve gastrectomy group.

Body weight changes during the postoperative period

The average weight of the animals in the first postoperative week was 395.1 g in the C group and 358.7 g in the vertical gastrectomy group (P = .006). After 4 weeks/28 days of postoperative follow-up, the animals reached an average weight of 436.6 and 391.6 g, respectively, in the C and SG groups (P = .001).

The results of the statistical analysis using Student's t-test are described in Table 1. The evolution of the average body weight during the postoperative follow-up is shown in Figure 1, and the descriptive analysis with a comparison of medians is presented in Figure 2.

FIG. 2.

Boxplot 1: Preoperative glucose level (median and IQR), sham group.

Glycemic control

The mean fasting blood glucose level of the animals before the start of obesity induction was 86.6 mg/dL in the C group and 88.7 mg/dL in the vertical gastrectomy group, with all animals having fasting blood glucose values below 100 mg/dL. After 4 weeks/28 days of feeding with the hypercaloric CAF, the mean fasting blood glucose level was 103.1 and 101.8 mg/dL, respectively, in the C and SG groups (Figure 2).

The increase in fasting blood glucose during the induction period was equivalent in all groups (P = .879). Results of the statistical analysis using Student's t-test are described in Figure 2.

In the fourth postoperative week, the SG group showed a decrease in the mean fasting blood glucose level with a value of 91.3 mg/dL, while the C group showed an elevation in this mean with a value of 109.4 mg/dL (P = .029). Results of the statistical analysis using Student's t-test are described in Table 2.

Table 2.

Mean Comparisons of Fasting Glucose Levels in mg/dL

Assessment time points	SG	SD	Control	SD	P
Initial week	88.7	± 5.1	86.6	± 3.2	.285
Fourth preoperative week	101.8	± 19.9	103.1	± 17.8	.879
Fourth postoperative week	91.3	± 12.7	109.4	± 20.5	.029

Control, control/sham group; SD, standard deviation; SG, sleeve gastrectomy group.

Discussion

Cafeteria diet

The CAF protocol for inducing obesity and glycemic alterations adapted by the Experimental Surgery Laboratory of the Federal University of Maranhão, used in this experiment, was designed to mimic human obesity-causing habits, with a diversified solid and liquid component, including soft drinks. The diet used in this experiment offers a variety of palatable foods with high glycemic and energy indexes, leading to an increase in food intake and, consequently, body weight gain and elevation of blood glucose levels.

Another relevant aspect of this protocol is the inclusion of a hypercaloric liquid component, which along with other foods rich in lipids and carbohydrates, further resembles a human diet when compared with models that increase energy intake solely through an overload of fat or carbohydrates.²⁹ The hypercaloric liquid component, soda, significantly increased the caloric intake of the diet (53.1 kcal/100 mL). CAFs with hypercaloric liquids have been used in experiments^30,31 to study various diseases and obesity-related consequences, but not in bariatric surgery.

Thus, the model used in this study proved to be effective in inducing obesity and elevating blood glucose levels. After the 28-day/4-week period, all animals developed obesity and were ready for the study. There was 100% effectiveness in inducing obesity, and there was a significant variation in the glycemic index in both groups, with 40% of the animals presenting fasting blood glucose values above 100 mg/dL.

Vertical gastrectomy and alteration of body weight in the postoperative period

The performance of vertical gastrectomy occurred without complications, affirming the effectiveness of replicating this operation in experimental rat surgery safely and with a low rate of postoperative complications.

After vertical gastrectomy, weight loss occurred only in the first postoperative week, while from the second week onward, the animals began to regain weight, reaching a similar weight as at the time of surgery at the end of 8 weeks.

A noteworthy aspect is maintenance of the CAF throughout the experiment, with the hypercaloric liquid component from the soft drink allowing a significant caloric intake for the animals even with the restrictive component of the surgery. This was evident by an increase in soft drink consumption and decrease in water consumption in the SG group.

Another important aspect is the comparison between the SG group and the C group, as animals that only underwent sham surgery showed a linear weight gain throughout the experiment, confirming the restrictive role of vertical gastrectomy in controlling excess weight, which did not occur in the C group, resulting in a significant difference in weight between the two groups (P = .001).

With the obtained data, this study confirms the replicability of vertical gastrectomy in the laboratory. Current experimental research with SG not only aims to demonstrate and elucidate its effectiveness in controlling obesity and associated comorbidities but also focuses on the postoperative repercussions of the surgery. Studies evaluating gastroesophageal reflux^32,33 provide examples of such research; thus, this work confirms the replicability of this surgery in the laboratory.

However, our results differ from those found in the literature, which show weight loss after vertical gastrectomy, both in studies performed without staplers/mechanical sutures^34–36 and those performed with the use of mechanical sutures.^37,38 The significant difference between this study and those reported in the literature is the inclusion of the hypercaloric liquid component in the CAF protocol used in this experiment, which may explain the divergent results found.

Glycemic control in the postoperative period

The analysis of postoperative glycemia showed that SG was able to reduce glycemic levels in animals in this group, while glycemic levels in animals subjected only to sham surgery were even higher after the 4-week postoperative follow-up, showing a statistically significant difference between the two groups (P = .029).

Therefore, the weight regain found in all animals subjected to vertical gastrectomy and the evidence of glycemic control despite weight loss in this experiment serve as stimuli for further research in this area, opening up the possibility of exploring the metabolic effects of vertical gastrectomy, particularly independently of weight loss.

The metabolic role of this procedure has been the subject of various experimental studies found in the literature,^35,39,40 which indicate an increase in gastric emptying time and stimulation of the distal ileum, resulting in increased GLP1 as the main post-SG metabolic mechanism. However, these studies did not involve obesity induction and weight regain in the postoperative period and they used animals with congenital diabetes mellitus to evaluate the metabolic effects of SG.

Conclusions

Vertical gastrectomy in rats is a feasible intervention.

The CAF allows for obesity induction and changes in glycemia in experimental animals.

Vertical gastrectomy enabled glycemic control in rats with obesity induced by the CAF.

Footnotes

Authors' Contributions

D.D.d.M. and O.G.F. were responsible for conceptualization, conducting the study, and writing of the draft.

R.M.d.A.L. was responsible for statistical analysis and writing of the draft.

B.Z. was responsible for writing of the draft and supervision.

Disclosure Statement

No competing financial interests exist.

Funding Information

The work was self-funded.

References

Volaco

, Tofolo

, Ferreira

SRG

, et al. Socioeconomic status: The missing link between obesity and diabetes mellitus?. Curr Diabetes Rev, 2018; 14(4):321–326; doi: 10.2174/1573399813666170621123227

Engin

The Definition and Prevalence of Obesity and Metabolic Syndrome. In: Obesity and Lipotoxicity: Advances in Experimental Medicine and Biology. Springer; 2017; pp. 1–17.

Park

, Cho

, Yoon

, et al. Comparative efficacy of bariatric surgery in the treatment of morbid obesity and diabetes mellitus: A systematic review and network meta-analysis. Obes Surg, 2019; 29,(7):2180–2190.

Stroud

, Stucke

Diabetes as an Indication for Bariatric Surgery. In: Difficult Decisions in Surgery: An Evidence-Based Approach. Springer, Cham; 2021; pp. 25–38.

Josemberg

, Ramos

, Galvao-Neto

, et al. The role of metabolic surgery for patients with obesity grade I and type 2 diabetes not controlled clinically. Arq Bras Cir Dig, 2016; 29(1):102–106; doi: 10.1590/0102-6720201600a10025

Bertoluci

, Rocha

, Souza

JRM

, et al. Diretriz Oficial da Sociedade Brasileira de Diabetes. Conectando Pessoas; 2022.

Shaw

, Sicree

, Zimmet

. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract, 2010; 87(1):4–14; doi: 10.1016/j.diabres.2009.10.007

World Health Organization. Global Report on Diabetes. WHO Library Cataloguing-in-Publication Data;. 2016, Vol. 978.

Maggio

, Pi-Sunyer

. Obesity and type 2 diabetes. Endocrinol Metab Clin North Am, 2003; 32(4):805–822; doi: 10.1016/s0889-8529(03)00071-9

10.

Updated position statement on sleeve gastrectomy as a bariatric procedure. Surg Obes Relat Dis, 2012; 8(3):e21–e26; doi: 10.1016/j.soard.2012.02.001

11.

Peterli

, Borbély

, Kern

, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: A randomized, prospective trial. Obes Surg, 2012; 22,(5):740–748. doi: 10.1007/s11695-012-0622-3

12.

Andriani

, Mansur

. A gastroplastia em manga (sleeve gastrectomy) e o diabetes mellitus. Arq Bras Cir Dig, 2008; 21(3):133–135; doi: 10.1590/S0102-67202008000300008

13.

Pinto Júnior

DAC

, Souza

, Amaral

, et al. Cafeteria diet intake for fourteen weeks can cause obesity and insulin resistance in Wistar rats. Rev Nutr, 2012; 25(3):313–319; doi: 10.1590/S1415-52732012000300001

14.

Fernandes

, Fagundes

, Bertolini

GRF

. Animal models of obesity in rodents: An integrative review. Acta Cir Bras, 2016; 31(12):840–844; doi: 10.1590/s0102-865020160120000010

15.

Cesaretti

MLR

, Colodel

, Pontes

EFBA

, et al. Modelos experimentais de resistência à insulina e obesidade: lições aprendidas. Arq Bras Endocrinol Metab, 2006; 50(2):190–197; doi: 10.1590/S0004-27302006000200005

16.

Bruinsma

, Uygun

, Yarmush

, et al. Surgical models of Roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice. Nat Protoc, 2015; 10(3):495–507; doi: 10.1038/nprot.2015.027

17.

Fernandes

, Fagundes

, Bertolini

GRF

. Animal models of obesity in rodents: An integrative review. Acta Cir Bras, 2016; 31,(12):840–844.

18.

Cesaretti

MLR

, Colodel

, Pontes

EFBA

, et al. Modelos experimentais de resistência à insulina e obesidade: Lições aprendidas. Arq Bras Endocrinol Metab, 2006; 50,(2):190–197.

19.

Bruinsma

, Uygun

, Yarmush

, et al. Surgical models of Roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice. Nat Protoc, 2015; 10,(3):495–507.

20.

Castelan F°

, Amaral

, Gragnani

, et al. Sleeve gastrectomy model in Wistar rats. Obes Surg, 2007; 17(7):957–961; doi: 10.1007/s11695-007-9150-y

21.

Gadiot

, Biter

, Zengerink

, et al. Long-term results of laparoscopic sleeve gastrectomy for morbid obesity: 5 to 8-year results. Obes Surg, 2017; 27(1):59–63; doi: 10.1007/s11695-017-2655-0

22.

Grong

, Glomsaker

, Hoff

DAL

, et al. The effect of duodenojejunostomy and sleeve gastrectomy on type 2 diabetes mellitus and gastrin secretion in Goto-Kakizaki rats. Surg Endosc, 2014; 29(3):723–733; doi: 10.1007/s00464-014-3732-2

23.

, Yin

, Wang

, et al. Sleeve gastrectomy provides a better control of diabetes by decreasing ghrelin in the diabetic Goto–Kakizaki rats. J Gastroint Surg, 2009; 13(12):2302–2308; doi: 10.1007/s11605-009-0997-1

24.

Chambers

, Jessen

, Ryan

, et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology, 2011; 141(3):950–958; doi: 10.1053/j.gastro.2011.05.050

25.

Wilson-Perez

, Chambers

, Ryan

, et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like peptide 1 receptor deficiency. Diabetes, 2013; 62(7):2380–2385; doi: 10.2337/db12-1498

26.

Kleinert

, Clemmensen

, Hofmann

, et al. Animal models of obesity and diabetes mellitus. Nat Rev Endocrinol, 2018; 14(3):140–162; doi: 10.1038/nrendo.2017.161

27.

Percie du Sert

, Ahluwalia

, Alam

, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol, 2020; 18(7):e3000410; doi: 10.1111/bph.15193

28.

Rosini

, Martins

, Fernandes

, et al. Obesidade induzida por consumo de dieta: modelo em roedores para o estudo dos distúrbios relacionados com a obesidade. Rev Ass Med Bras, 2012; 58(3):383–387; doi: 10.1590/S0104-42302012000300021

29.

Massone

Técnicas anestésicas em animais de pequeno e médio porte. In: Anestesiologia Veterinária—Farmacologia e Técnicas. 3^a ed. Rio de Janeiro; 1999; pp. 791–797.

30.

Beilharz

, Maniam

, Morris

. Cafeteria diet and probiotic therapy: Cross talk among memory, neuroplasticity, serotonin receptors and gut microbiota in the rat. Mol Psychiatry, 2018; 23(2):351–361; doi: 10.1038/mp.2017.38

31.

Lewis

, Knezovic

, Blennerhassett

, et al. Cafeteria-diet induced obesity results in impaired cognitive functioning in a rodent model. Heliyon, 2019; 5(3):e01412; doi: 10.1016/j.heliyon.2019.e01412

32.

Gimenez

, Romaozinho

, Guimaraes

, et al. Gastrectomia vertical com piloroplastia em ratos Wistar: Avaliação do esvaziamento gástrico, do trânsito intestinal e do possível refluxo alcalino duodeno-gástrico. Tese (Doutorado em Clínica Cirúrgica)—Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto;, 2022; doi: 10.11606/T.17.2022.tde-08082022-094056\

33.

Valadão

, Saadi

, Valezi

, et al. Gastrectomia vertical vs. Gastrectomia vertical ampliada: Qual o impacto na doença do refluxo gastroesofágico em ratos obesos?. Arq Bras Cir Dig, 2020; 33(2):e1513; doi: 10.1590/0102-672020190001e1513

34.

Kodama

, Gotohda

, Mano

, et al. Eating behavior in rats subject to vagotomy, sleeve gastrectomy and duodenal switch. J Gastroint Surg, 2010; 14(9):1502–1510; doi: 10.1007/s11605-010-1315-7

35.

Lopez

, Nicholson

, Burkhardt

, et al. Development of a sleeve gastrectomy weight-loss model in obese Zucker rats. J Surg Res, 2009; 157(2):243–250; doi: 10.1016/j.jss.2008.10.025 36

36.

Valentí

, Cienfuegos

, Becerril

, et al. Sleeve gastrectomy induces weight loss in diet-induced obese rats even if high-fat feeding is continued. Obes Surg, 2011; 21(9):1438–1443; doi: 10.1007/s11695-010-0277-x

37.

Patrikakos

, Toutouzas

, Perrea

, et al. A surgical rat model of sleeve gastrectomy with staple technique: Long-term weight loss results. Obes Surg, 2009; 19(12):1586–1590; doi: 10.1007/s11695-009-9965-9

38.

Saedi

, Gheissari

, Afghani

, et al. Sleeve gastrectomy and roux-en-y gastric bypass exhibit differential effects on food preferences, nutrients absorption, and energy expenditure in obese rats. Int J Obes, 2012; 36(11):1396–1402; doi: 10.1038/ijo.2012.167

39.

Chambers

, Smith

, Begg

, et al. Regulation of gastric emptying rate and its role in nutrient-induced GLP-1 secretion in rats after vertical sleeve gastrectomy. Am J Physiol Endocrinol Metab, 2013; 306(4):E424–E432; doi: 10.1152/ajpendo.00469.2013

40.

Trung

, Lam

, Le

DTH

, et al. Effect of sleeve gastrectomy on body weight, food intake, glucose tolerance, and metabolic hormone level in two different rat models: Goto-Kakizaki and diet-induced obese rat. J Surg Res, 2013; 185(1):159–165; doi: 10.1016/j.jss.2013.05.019