DIFFERENTIAL REGULATION OF INHIBIN SUBUNITS BY GERM CELLS IN HUMAN TESTES

Inhibin B is comprised of two dissimilar disulfide-linked subunits, termed α and βB, and is physiologically more important than inhibin A in the male. The aim of this study was to investigate testicular expression of inhibin subtypes in infertile men to uncover any interaction between Sertoli cells and germ cells. Ten azoospermic patients with Sertoli cell only syndrome (SCO) and 39 oligozoospermic men were included in this study. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations were determined by chemiluminescence assays. The serum concentrations of inhibin B were measured by enzyme-linked immunosorbent assay. Immunohistochemical staining for the α-subunit, β A-subunit, and βB-subunit of inhibin were performed on testicular biopsy specimens. The results were that serum inhibin B was undetectable in azoospermic men with SCO, while it was 133.8?±?82.0?pg/ml in oligozoospermic men. There was little expression of βA in the testes of any patient. Expression of inhibin α and βB was observed in Sertoli cells. The percentage of Sertoli cells expressing inhibin α was similar in azoospermic patients with SCO (55.3%?±?20.6%) and in oligozoospermic patients (42.8%?±?30.4%). In contrast, expression of βB in Sertoli cells of azoospermic patients (24.9%?±?16.8%) was lower than in oligozoospermic men (43.4%?±?25.5%: P?=?0.0308). There are no significant correlations between testicular expression of inhibin βB and the serum inhibin B concentrations. The expression of inhibin βB by Sertoli cells is dependent on the coexistence of spermatogenic activity within these seminiferous tubules, explaining why the level of inhibin B is low in patients with SCO.     

CONTROL OF SPERMATOGENESIS IN PRIMATE AND PROSPECT OF MALE CONTRACEPTION

The present review is a summary of mechanisms of spermatogenesis in primates with emphasis on anti-spermatogenesis of testosterone (T), gossypol, and “testicular heat stress” for development of male contraception. Both FSH and testosterone stimulate all phases of spermatogenesis. FSH is capable of amplifying the population of the differentiated spermatogonia (B1, B2, B3 and B4) and controls the spermatogonia production rate, and, in synergy with testosterone, regulating spermatogenesis in adult monkeys. Pituitary FSH beta gene expression is governed by a feedback of Beta inhibin, which is a major component of the testicular negative feedback signals. Beta inhibin secreted by Sertoli cells is in turn inhibited by testosterone from Leydig cells under the control of LH. Disturbance of the normal interaction of pituitary FSH with Sertoli cell Beta inhibin is responsible for azoospermia or oligozoospermia induced by exogenous T. Three possible regimens of T, gossypol and “heat stress” have been suggested for male contraception. They act on different sites and stages of spermatogenesis in testis or sperm activity in epididymis. Apoptosis induced by testosterone occurs mainly at stages VII–VIII of spermatogenesis while that by testicular “heat stress” mostly occurs at stages I–IV and X–XII. Low dose of gossypol mainly influences the sperm activity in the epididymis although it also acts on testicular spermatids.     

ADAMTS1 and ADAMTS5 metalloproteases produced by Sertoli cells: a potential diagnostic marker in azoospermia

In this study, our aim was to detect protein levels of A Disintegrin and Metalloproteinase with Thrombospondin Motifs 1 and 5 (ADAMTS1 and ADAMTS5) proteases and to examine the effect of in vitro FSH supplementation on protease production in cultured Sertoli cells. The expression of metalloproteases, ADAMTS1, and ADAMTS5 were investigated in Sertoli cell cultures as well as in ejaculate of azoospermic men which then were compared with ejaculates of the fertile control group. A total of 15 azoospermic men, diagnosed as obstructive (OA, n = 5) and nonobstructive (NOA, n = 10) azoospermia were included in the study. ADAMTS1, ADAMTS5 and FSH receptors (FSHR) were found to be expressed 2.56, 2.10, and 2.66-fold less in Sertoli cells of NOA patients, than those of OA (p < 0.05). After rFSH was added onto Sertoli cell cultures of NOA patients, their expression did not increase significantly and did not reach to levels of control group. Evaluation of ejaculates revealed that the expression of ADAMTS1 and ADAMTS5 were insignificantly 1.03 and 1.1-fold higher in OA group (p > 0.05), respectively; however, in the NOA group, their expression were 1.70 and 1.96-fold lower, respectively, when compared with the fertile control group (p < 0.05) which was statistically significant. As a conclusion, the present study has revealed that insufficiency of ADAMTS1 and ADAMTS5 expression in Sertoli cells may have an important role in the etiology of male infertility. As expected due to low FSHR expression, rFSH response is impaired in NOA patients with relatively low ADAMTS expression response; therefore, such patients might hardly benefit from rFSH treatment. Further studies with larger cohorts may reveal ADAMTSs’ potential use as a predictive marker for positive sperm retrieval in azoospermic patients who are scheduled to undergo testicular sperm extraction.

Abbreviations: ADAM: A Disintegrin and Metalloproteinase; ADAMTS1 and ADAMTS5: A Disintegrin and Metalloproteinase with 10 Thrombospondin Motifs 1 and 5; ADAMTS: A Disintegrin and Metalloproteinase with Thrombospondin; ABP: androgen binding protein; CAMs: cell adhesion molecules; ECM: extracellular matrix; FSH: follicle stimulating hormone; FSHR: FSH receptors; HRP: horseradish peroxidase; MMP: matrix metalloproteinases; MP: metalloproteinases; NOA: nonobstructive azoospermia; OA: obstructive azoospermia; TIMP-1: tissue inhibitor of metalloproteinase-1     

Heme Iron Concentrate and Iron Sulfate Added to Chocolate Biscuits: Effects on Hematological Indices of Mexican Schoolchildren

Objective: Food fortification is one of the most effective strategies for increasing iron intake in the population. A simple blind trial was conducted to compare the effect of 2 forms of iron fortification and assess the changes in hemoglobin and iron status indices among preschool children from rural communities.

Methods: Hemoglobin was evaluated in 47 children aged 3–6 years old. For 72 days (10-week period), children ate Nito biscuits. Thirteen pupils with elevated hemoglobin levels were assigned to the biscuit control group, and pupils with hemoglobin equal to 13.5 mg/dL or less were randomly allocated to consume fortified biscuits with a heme iron concentrate (n = 15) or iron sulfate (n = 19). Changes in hemoglobin, plasma ferritin, and other hematological indices were evaluated with analysis of variance (ANOVA) for repeated measurements.

Results: Except mean corpuscular hemoglobin concentrations (+1.27 ± 2.25 g/dL), hematological indices increased significantly across the study: Mean corpuscular volume (+2.2 ± 1.0 f/dL), red blood cells (+0.30 ± 0.37 M/μL), mean corpuscular hemoglobin (+1.8 ± 1.74 pg), hemoglobin (+1.68 ± 0.91 g/dL), hematocrit (+3.43% ± 3.03%), and plasma ferritin (+18.38 ± 22.1 μg/L) were all p < 0.05. After 10 weeks, the adjusted effect of the iron-fortified chocolate biscuits in the hemoglobin levels was higher than the control group (+1.1 ± 0.2 g/dL) but no difference was found between consumers of fortified biscuits with heme iron concentrate or iron sulfate (+1.9 ± 0.2 g/dL and +2.0 ± 0.2 g/dL, respectively).

Conclusion: Heme iron concentrate and iron sulfate were equally effective in increasing Hb levels and hematological indices. Processed foods were shown to be an effective, valuable, and admissible intervention to prevent anemia in preschool children.     

抑制素B对精子发生障碍的诊断参考价值

抑制素B是睾丸分泌的一种糖蛋白激素,受垂体卵泡刺激素(FSH)特异调控,具有昼夜分泌节律性并随年龄增加而变化。成年男性抑制素B几乎全部来自于睾丸,且其组装过程大部分在生精细胞内完成,而后释放到循环和精浆,因此血清和精浆抑制素B水平与精子发生同步。由于使用高特异性抗体,酶联免疫吸附法（双抗体夹心ELISA法）可精确测定具有生物活性的抑制素B,满足科研和临床的需要。抑制素B的浓度在精子发生障碍时会出现变化,通过测定其浓度可对精子发生状态作出评估,在鉴别梗阻性与非梗阻性无精子症方面也具有较高的特异性与敏感性。     

The Effects of Fortetropin Supplementation on Body Composition,Strength, and Power in Humans and Mechanism of Action in a Rodent Model

Objective: The purpose of this study was to investigate the effects of Fortetropin on skeletal muscle growth and strength in resistance-trained individuals and to investigate the anabolic and catabolic signaling effects using human and rodent models.

Methods: In the rodent model, male Wistar rats (250 g) were gavage fed with either 1.2 ml of tap water control (CTL) or 0.26 g Fortetropin for 8 days. Then rats participated in a unilateral plantarflexion exercise bout. Nonexercised and exercised limbs were harvested at 180 minutes following and analyzed for gene and protein expression relative to mammalian target of rapamycin (mTOR) and ubiquitin signaling. For the human model, 45 (of whom 37 completed the study), resistance-trained college-aged males were divided equally into 3 groups receiving a placebo macronutrient matched control, 6.6 or 19.8 g of Fortetropin supplementation during 12 weeks of resistance training. Lean mass, muscle thickness, and lower and upper body strength were measured before and after 12 weeks of training.

Results: The human study results indicated a Group × Time effect (p ≤ 0.05) for lean mass in which the 6.6 g (+1.7 kg) and 19.8 g (+1.68 kg) but not placebo (+0.6 kg) groups increased lean mass. Similarly, there was a Group × Time effect for muscle thickness (p ≤ 0.05), which increased in the experimental groups only. All groups increased equally in bench press and leg press strength. In the rodent model, a main effect for exercise (p ≤ 0.05) in which the control plus exercise but not Fortetropin plus exercise increased both ubiquitin monomer protein expression and polyubiquitination. mTOR signaling was elevated to a greater extent in the Fortetropin exercising conditions as indicated by greater phosphorylation status of 4EBP1, rp6, and p70S6K for both exercising conditions.

Conclusions: Fortetropin supplementation increases lean body mass (LBM) and decreases markers of protein breakdown while simultaneously increasing mTOR signaling.     

Leptospira seropositivity as a risk factor for Mesoamerican Nephropathy

Background: Leptospirosis is postulated as a possible cause of Mesoamerican Nephropathy (MeN) in Central American workers.

Objectives: Investigate job-specific Leptospira seroprevalence and its association with kidney disease biomarkers.

Methods: In 282 sugarcane workers, 47 sugarcane applicants and 160 workers in other industries, we measured anti-leptospiral antibodies, serum creatinine, and urinary injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and N-acetyl-D-glucosaminidase (NAG).

Results: Leptospira seroprevalence differed among job categories and was highest among sugarcane cutters (59%). Seropositive sugarcane workers had higher NGAL concentrations (relative mean: 1.28; 95% CI: 0.94–1.75) compared to those who were seronegative, with similar findings among field and non-field workers.

Conclusions: Leptospira seroprevalence varied by job category. There was some indication that seropositivity was associated with elevated biomarker levels, but results were inconsistent. Additional studies may help establish whether Leptospira infection plays any role in MeN among Central American workers.     

Testis functions and sexual potentia in langur monkey treated with a combination steroidal contraceptive formulation

Administration of a combination formulation of danazol (100 mg/day; oral) plus testosterone enanthate (TE) (50 mg/15 days; i.m.) for 30 to 60 days in adult male langur monkeys resulted in the reversible suppression of testicular function without affecting the sexual potentia. Testicular weight and volume decreased significantly along with the mass atrophy of germinal epithelium and impaired morphology of Leydig and Sertoli cells. A conspicuous shrinkage of seminiferous tubules, Leydig cell nuclei and Sertoli cell nuclei was noted. Elevation of testicular cholesterol, total lipids, glycogen and phosphatases activity with the depletion of total proteins, nucleic acid, sialic acid and fructose was noteworthy. All changes were maintained during maintenance dose studies (danazol: 50 mg/day; oral plus TE: 50 mg/15 days; i.m.) for 60 days. Resumption of all measures to normal was evident following 120 days of recovery. It can be concluded that the exogenous TE substitutes the serum testosterone levels to maintain extratesticular androgen actions even after interference by danazol of Leydig cell function along with spermatogenesis inhibition.     

Bio-monitoring of DNA damage in matchstick industry workers from Peshawar Khyber Pakhtunkhwa,Pakistan

Background: Safety protocols are usually neglected in most of the matchstick industries rendering the laborer prone to various occupational hazards.

Objective: The present study highlights DNA damage among matchstick factory workers (n = 92) against a control group (n = 48) of healthy individuals.

Methods: Genotoxicity was measured in peripheral blood lymphocytes of the test subjects using a Single Cell Gel Electrophoresis assay (SCGE/comet assay).

Results: Our results substantiate a high Total Comet Score (TCS) for factory workers (74.5 ± 47.0) when compared to the control group (53.0 ± 25.0) (P ≤ 0.001). Age and duration of occupational exposure had no significant effect (P > 0.05) on TCS value. As for job function, the TCS value was greatest in sweepers (91.0 ± 56.1) and lowest in box-making operators (26.0 ± 25.0) indicating that waste disposal poses the higher risk of DNA damage.

Conclusions: Our study corroborates that matchstick chemicals can potentially damage the DNA of exposed subjects.     

Vitamin D Deficiency in Pregnant Ukrainian Women: Effects of Alcohol Consumption on Vitamin D Status

Objective: Heavy alcohol consumption can alter vitamin D status; however, the relationships between alcohol consumption and vitamin D concentrations in pregnant women have not been well studied. The aim of this study was to investigate the vitamin D status in a population of alcohol-exposed (N = 180) and low/unexposed control (N = 179) Ukrainian pregnant women.

Methods: Women who attended prenatal care facilities in 2 regions of Ukraine (Rivne and Khmelnytsky) for a routine prenatal visit were screened for the study. At the time of enrollment (20.4 ± 7.0 weeks of gestation), blood samples and alcohol consumption data (during a typical week around conception and the most recent 2 weeks) were collected. Vitamin D status was assessed by 25-hydroxyvitamin D [25(OH)D] concentrations.

Results: A high prevalence of suboptimal vitamin D status in pregnant Ukrainian women was observed. Overall, 50.1% and 33.4% of the women were classified as vitamin D deficient [25(OH)D < 20 ng/mL] or insufficient [25(OH)D ≥ 20 ng/mL and ≤30 ng/mL], respectively, based on 2011 Endocrine Society guidelines. Alcohol-exposed women had significantly lower 25(OH)D concentrations than low/unexposed women in Spring (p = 0.006) and Winter (p = 0.022). When vitamin D concentrations were grouped into sunny season (Summer + Fall) compared to not sunny season (Winter + Spring), there was a significant ethanol by season interaction (p = 0.0028), with alcohol-drinking women having lower circulating vitamin D compared to low/unexposed women in seasons of low sun availability.

Conclusions: These data suggest that when vitamin D concentrations are generally low (e.g., during seasons of low sun availability), alcohol consumption during pregnancy has a negative impact on vitamin D status.     

Determination of serum carbamazepine concentration using dried blood spot specimens for resource-limited settings

Objectives: Carbamazepine (CBZ) is a commonly used anti-epileptic in rural hospitals in India. These hospitals lack the facilities to measure CBZ concentration; however, in larger hospitals this is performed using high performance liquid chromatography (HPLC). Dried blood spot (DBS) represents a feasible matrix for safe transportation by post/courier. This study was to determine whether the concentration of CBZ in serum can be predicted from that measured in DBS using an inexpensive HPLC method and inexpensive standard filter paper.

Methods: CBZ in serum and DBS from 80 epileptic patients were measured using a validated HPLC assay. The data was then randomly divided into two groups; simple Deming regression was performed with the first group and validation was performed using the second.

Results: There was a good correlation between the serum and DBS concentrations (r = 0.932) in the first group. The regression equation obtained was: predicted serum concentration = DBS concentration x 0.83 + 1.09. In the validation group, the correlation between the predicted and actual serum concentrations was also good (r = 0.958), and the mean difference between them was only 0.28 μg/ml (p = 0.8062). The imprecision and bias in both the groups were acceptable.

Conclusion: Using inexpensive materials, serum CBZ concentrations can be accurately predicted from DBS specimens. This method can be recommended for the therapeutic drug monitoring of CBZ in resource-limited settings.     

Antidiabetic Effect of Rosella-Stevia Tea on Prediabetic Women in Yogyakarta,Indonesia

Background: Rosella tea (Hibiscuss sabdariffa. Linn) with stevia sweetener (Stevia rebaudiana Bertoni) is a combined herbal drink that is expected to have antidiabetic effect by lowering glucose levels in people with diabetes and prediabetes. This research investigates the effect of rosella-stevia tea to decrease fasting blood glucose (FBG) and 2 hours postprandial blood glucose (2-hour postprandial BG) level in prediabetic women.

Method: This is quasi-experimental research with control and treatment (rosella-stevia tea) group. Each group consists of 12 prediabetic women aged 30–60 years. Rosella-stevia tea (5 g rosella powder, 125 mg stevia sweetener) was administered to the treatment group twice a day for 14 days.

Result: Rosella-stevia tea consumption affects blood glucose levels. Rosella-stevia tea consumption significantly lowered the FBG level (from 111.25 ± 7.20 mg/dL to 88.58 ± 13.19 mg/dL; p < 0.01) but not the 2-hour postprandial BG level (from 123.25 ± 37.61 mg/dL to 106.92 ± 18.82 mg/dL). There are no significant differences in the control group (FBG level from 106.00 ± 5.27 mg/dL to 102.08 ± 8.36, and 2-hour postprandial BG level from 119.83 ± 16.43 mg/dL to 128.00 ± 23.54 mg/dL).

Conclusion: Rosella-stevia tea consumption can lower the FBG level but not the 2-hour postprandial BG level in prediabetic women.     

Assessment of exposure to pesticides during mixing/loading and spraying of tomatoes in the open field

Some evidence of exposure-response of metolachlor and pendimethalin for lung cancer and an association of metribuzin with risk of glioma have been reported. The primary objectives in this study were to evaluate exposure and occupational risk during mixing/loading of pesticides and during their application to tomatoes cultivated in open fields.

Sixteen farmers were sampled. Respiratory exposure was estimated by personal air sampling using fiberglass filters in a IOM device. Dermal exposure was assessed using skin pads and hand washing. Absorbed doses were estimated assuming 100% lung retention, and 50% or 10% skin absorption for metribuzin, and pendimethalin and metolachlor, respectively. The three pesticides were quantified by gas chromatography tandem mass spectrometry in all matrices. Metolachlor was used as a tracer of contamination of clothes and tractors unrelated to the exposure monitored.

Respiratory exposure to metribuzin, used in granular form, was on average more than one order of magnitude higher than exposure to pendimethalin, used in the form of microencapsulated liquid. The actual doses were 0.067–8.08 µg/kg bw, 0.420–12.6 µg/kg bw, and 0.003–0.877 µg/kg bw for pendimethalin, metribuzin, and metolachlor, respectively. Dermal exposure was about 88% of the actual dose for metribuzin and more than 95%, for pendimethalin and metolachlor. For risk assessment, the total absorbed doses (sum of respiratory and skin absorbed doses) were compared with the AOEL for each compound.

The actual and absorbed doses of the three pesticides were always lower than the acceptable operator exposure level (AOEL), which are reported to be 234 µg/kg bw, 20 µg/kg bw, and 150 µg/kg bw for pendimethalin, metribuzin, and metolachlor, respectively. In any case, personal protective equipment and spraying devices should be chosen with care to minimize exposure.     

SERUM INHIBIN PRO αC IN INFERTILE MEN

Specific assays have been developed for bioactive inhibin dimers, inhibin A and B, and inhibin &#102 -subunit precursor pro &#102 C. To better understand the role of serum inhibin pro &#102 C in infertile men, the authors measured these forms of inhibin in sera from 39 infertile men and analyzed inhibin relationships with serum gonadotropins, testosterone, and estradiol. All subjects had oligozoospermia. Inhibin A levels were undetectable in all subjects. Inhibin B concentrations were 117 &#45 59 pg/mL. Inhibit B concentrations correlated negatively with serum FSH ( r =. 584, p <. 0001) and positively with sperm count ( p <. 01) and bilateral testicular volume ( r =. 607, p <. 0001). The concentration of pro &#102 C was 556 &#45 236 pg/mL (normal range, 446 &#45 28). Inhibin pro &#102 C showed no correlation with serum FSH, LH, testosterone, sperm concentration, and bilateral testicular volume. In addition, inhibin pro &#102 C was not correlated with inhibin B. Pro &#102 C is unlikely to be a useful marker for spermatogenesis in infertile men compared with inhibin B.     

Impaired serotonin communication during juvenile development in rats diminishes adult sperm quality

Spermatogenesis and steroidogenesis are testicular functions regulated by gonadotrophins as well as other factors, including serotonin. Testicular serotonin acts as an autocrine regulator of testosterone secretion, but studies on its role in spermatogenesis and sperm quality are scarce. Here, we analyzed the effects of intratesticular inhibition of serotonin synthesis on gonadotrophins, testosterone, and sperm quality. Both testicles of 30-day-old rats were injected once with saline solution (SS) or distinct concentrations of p-chloroamphetamine (PCA) (0.03, 0.06, or 0.12 mg). At 65 days of age, rats were euthanized and sperm density, motility, membrane integrity, mitochondrial function, and abnormalities were evaluated in gametes from the vas deferens. Inhibition of synthesis of intratesticular serotonin by PCA diminished the concentrations of testosterone and follicle-stimulating hormone (FSH) but luteinizing hormone (LH) levels were unaltered. Sperm density was not modified in animals injected with the different concentrations of PCA. In contrast, the percentage of sperm with abnormalities increased and the sperm membrane integrity decreased in animals injected at higher PCA concentrations. The functionality of sperm mitochondria in PCA-injected animals decreased only at the highest PCA dose. Our results indicate that testicular serotonin plays a role in testosterone synthesis and in the normal development of sperm, and blocking its effects disrupts the hormonal communication between the testis and hypophysis.

Abbreviations: SS: saline solution; PCA: p-chloroamphetamine; FSH: follicle-stimulating hormone; LH: luteinizing hormone; TPH: tryptophan hydroxylase; MAO: monoamine oxidase; AC: absolute control group; PI: propidium iodide; FLICA: fluorescence inhibitor of caspase; 3β-HSD: 3β-hydroxysteroid dehydrogenase; 17-KSR: 17-ketosteroid reductase; DHT: 5-dihydrotestosterone     

The Role of Eating Habits on the Iron Status of Pregnant Women

Objective: This study highlights the relationship between some eating habits and iron status during pregnancy.

Subjects: The study included 219 healthy pregnant women aged 27.6 ± 5.7 years from southern Bulgaria.

Methods: Subjects’ iron status was assessed on the basis of the following iron indicators: hemoglobin (Hb), serum ferritin (SF), serum transferrin receptor (sTfR), and body iron index (mg/kg).

Results: Severe anemia among the women from southern Bulgaria was not observed. Advanced pregnancy and some eating habits are factors that deteriorate iron status. Women who had consumed fish at least 3 times a week had lower levels of sTfR (р = 0.008), higher levels of SF (р = 0.05), and lower levels of body iron (р = 0.018). Frequent legume consumption was related to increased levels of sTfR (р = 0.036). Pregnant women with a high frequency of coffee consumption had lower values of body iron (р < 0.0001). Women who had consumed cow's milk at least 3 times a week had lower levels of SF (р = 0.026) and body iron (р = 0.042).

Conclusions: Regular consumption of fish and legumes, rarely drinking coffee, and milk consumption during the intervals between food intake are conditions for optimization of iron status during pregnancy.     

The Synergism in Hormonal and Cellular Changes in Male Mice on Long Term High Fat Exposure

Objective: To determine the hormonal changes that occur as a result of the long-term intake of a very-high-fat diet (VHFD) that leads to simultaneous changes in the islets of Langerhans and adipocyte cell size.

Methods: Male mice were fed with a normal chow diet (ND, n = 15) and a VHFD (n = 30) for 2, 12, and 24 weeks. Body weight, food intake, caloric intake (fat [saturated and unsaturated], protein, and carbohydrate), hormone levels (leptin and insulin), and islet of Langerhans/adipocyte size were quantitatively recorded.

Results: In VHFD-fed animals, body weight showed a significant percent increase within the first 12 weeks and then plateaued with time. VHFD-fed animals consumed significantly less food than ND at all time periods, indicating that it was the quality of food and not the quantity that caused this increase in body weight. Male mice on VHFD showed a significant increase in leptin and insulin levels, along with accompanying growth in islet and adipocyte size within the first 12 weeks, which plateaued as the mice aged. The increases in the islet and adipocyte size in VHFD-fed animals were similar to the analogous increases in hormonal levels (2 vs. 12 vs. 24 weeks). These results, therefore, suggest that in diet-induced obesity changes, shifts in hormonal levels works hand-in-hand with metabolic adjustments at the cellular level to combat the effect of fat.

Conclusion: Thus, mechanisms like hormonal resistance, changes in adiposity, islet size, and caloric intake with prolonged exposure to high fat are probably defensive mechanisms employed to protect against diabetes. In order to understand these complicated and nuanced effects of high fat and to comprehend the underlying mechanism associated with it, it is important to focus on long-term studies that emphasize the synergy between cellular and hormonal changes, in addition to an analysis of individual components.