Adipocyte Surface Area Research Articles

Dietary succinate reduces fat deposition through gut microbiota and lipid metabolism in broilers

Succinate has been shown to be a potentially beneficial nutritional supplement with a diverse range of physiological functions. However, it remains unknown whether succinate supplementation regulates lipid metabolism in chickens. The aim of this study was to explore how succinate affects fat deposition and the underlying mechanism involved in broilers and to determine the most appropriate level of succinate supplementation in the diet. A total of 640 one-day-old male yellow-feathered broilers were randomly divided into 4 groups with 8 replicates and 20 broilers per replicate. A basal diet was provided to the control group (CON). The experimental broilers were fed diets containing 0.2% (L), 0.4% (M), or 0.6% (H) succinate and the study was lasted for 21 d. The linear (l) and quadratic (q) effects of succinate addition were determined. The results indicated that supplementation with 0.4% succinate reduced ADFI, serum triglycerides (l, q; P < 0.05), glucose (q; P < 0.05), and increased high-density lipidprotein cholesterol (l, q; P < 0.05) concentrations in broilers. Moreover, 0.4% succinate affects lipid metabolism by decreasing the abdominal fat percentage and adipocyte surface area, the expression of genes that promote liposynthesis in the abdominal fat and liver, as well as increasing the expression of genes that promote lipolysis in the abdominal fat and liver. In addition, increased cecal propionic acid content (q, P < 0.05) was found in the M group compared to the CON group. The 16S rRNA sequence analysis showed that group M altered cecum microbial composition by increasing the abundance of genera such as Blautia and Sellimonas (P < 0.05). LC-MS metabolomic analysis revealed that the differential metabolites between the M and CON groups were enriched in amino acid-related pathways. In conclusion, the optimum level of succinate added to broiler diets in the present study was 0.4%. Succinate can potentially reduce fat accumulation in broilers by modulating the composition of the gut flora and amino acid metabolism related to lipid metabolism.

Influence of Maternal Diet and Intergenerational Change in Diet Type on Ovarian and Adipose Tissue Morphology in Female Rat Offspring.

Background and Objectives: A high-fat diet causes inflammation in the organism and many metabolic disorders. Adipose tissue secretes adipokines that affect the function of many organs. The health status of the mother before and during pregnancy affects the health of the offspring. The aim of this study was to determine how the type of maternal diet and the change in the type of diet in the offspring affects the histological characteristics of the ovaries and subcutaneous and perigonadal adipose tissue in female rat offspring. Materials and Methods: Ten female rats were divided into two groups. One group was fed standard laboratory chow, and the other was fed a high-fat diet and mated with a male of the same breed. The offspring of both groups of dams were divided into four subgroups with different feeding protocols. At 22 weeks of age, the offspring were sacrificed. Ovaries and subcutaneous and perigonadal adipose tissue were isolated. In the ovaries, the presence of cystic formations was investigated. Histomorphometric analysis was performed in two types of adipose tissue. Results: The weight of the ovaries of the offspring of mothers fed a high-fat diet was significantly higher than that of the offspring of mothers fed standard laboratory diets. Cystic formations were found in the ovaries of the offspring of mothers fed a high-fat diet. In subcutaneous adipose tissue, the percentage of small-sized adipocytes was significantly higher in the offspring of mothers fed standard laboratory diets. There were no significant differences in adipocyte surface area and adipocyte number between groups. Conclusion: Maternal diet influences the morphology of the ovaries and adipose tissue of the offspring.

The role of adiposity, body mass index, aging and chronic comorbidities on the progression of COVID-19 illness. Is a ‘long COVID’ syndrome inevitable?

Age associated overweight and obese conditions now approach epidemic proportions in Westernized society, often beginning in childhood and extending throughout the lifespan. Excess adiposity is often linked to increased visceral fat deposition where it is associated with increases in the relative risks for developing severe complications of covid-19. Thus, excess adiposity, along with NIDDM, hypertension, respiratory, disordered bioenergetics and other comorbidities, may be added to a growing list of significant independent risk factors in the progression of complications in covid-19 illness in both vaccinated and unvaccinated individuals, and which may lead to the development of a syndrome of ‘long covid’ in a sizable proportion of those infected. In addition to excess adiposity, non-insulin dependent diabetes (NIDDM), hypertension, disordered bioenergetics, along with other commonly occurring age-related comorbidities contribute to a lengthy list of significant risk factors that often progress to complications in the development and treatment options for covid-19 illness. These complications may occur in both vaccinated and unvaccinated individuals and may lead to the development of a syndrome of ‘long covid’ in a sizable proportion of infected individuals. The coronavirus causing Covid-19, SARS-CoV-2 has some similarities to the emergence of earlier reports of other zoonotic coronavirus illnesses including MERS and SARS which also caused respiratory illness in humans also with chronic symptoms of fatigue, musculoskeletal pain and psychiatric impairments. The origin of SARS-Cov-2 remains unclear, but appears to have originated in Wuhan, China in late 2019 as a local epidemic but within a few months had spread throughout the globe and was declared a pandemic by the WHO within three months of its first report to the WHO in December 2019. The virus enters mammalian organ systems via ACE2 receptors of receptive tissues of the respiratory, gastrointestinal, and other organs including the adipose tissue that can interact with the infective spike protein domains of the virus thereby permitting cellular entry. Once the adipose tissue becomes infected, the virus begins to replicate vigorously and initiates the release of inflammatory cytokines including IL-6, TNF and others which can contribute to an often-fatal cytokine storm. The common clinical symptoms include fever, coughing, musculoskeletal pain, and profound fatigue, and which often progress to hyperinflammation, a potentially serious cytokine storm, an acute respiratory distress syndrome (ARDS) and covid-related coagulopathy (CAC) and are often observed in overweight or obese individuals following SARS-CoV-2 infection in the absence of other comorbidities. While weight loss toward a normalization of BMI and an otherwise healthy weight is associated with smaller adipocyte size and corresponding adipocyte surface area can decrease the relative risks for other comorbidities over time, the risk reduction for COVID-19 following weight loss remains unclear. In conclusion, progressive increases in adiposity, overweight and obese conditions that increase visceral fat deposition and may progressively increase the relative risk for the most severe complications and dire outcomes of COVID-19 illness.

Histological and transcriptomic analysis of adipose and muscle of dairy calves supplemented with 5-hydroxytryptophan

In mammals, peripheral serotonin is involved in regulating energy balance. Herein, we characterized the transcriptomic profile and microstructure of adipose and muscle in pre-weaned calves with increased circulating serotonin. Holstein bull calves (21 ± 2 days old) were fed milk replacer supplemented with saline (CON, 8 mL/day n = 4) or 5-hydroxytryptophan (5-HTP, 90 mg/day, n = 4) for 10 consecutive days. Calves were euthanized on d10 to harvest adipose and muscle for RNA-Sequencing and histological analyses. Twenty-two genes were differentially expressed in adipose, and 33 in muscle. Notably, Interferon gamma inducible protein-47 was highly expressed and upregulated in muscle and adipose (avg. log FC = 6.5). Enriched pathways in adipose tissue revealed serotonin’s participation in lipid metabolism and PPAR signaling. In muscle, enriched pathways were related to histone acetyltransferase binding, Jak-STAT signaling, PI3K-Akt signaling and cell proliferation. Supplementation of 5-HTP increased cell proliferation and total cell number in adipose and muscle. Adipocyte surface area was smaller and muscle fiber area was not different in the 5-HTP group. Manipulating the serotonin pathway, through oral supplementation of 5-HTP, influences signaling pathways and cellular processes in adipose and muscle related to endocrine and metabolic functions which might translate into improvements in calf growth and development.

Early Childhood Fat Tissue Changes-Adipocyte Morphometry, Collagen Deposition, and Expression of CD163+ Cells in Subcutaneous and Visceral Adipose Tissue of Male Children.

Childhood obesity is a complex health problem, and not many studies have been done on adipose tissue remodeling in early childhood. The aim of this study was to examine extracellular matrix remodeling in the adipose tissue of healthy male children depending on their weight status. Subcutaneous and visceral adipose tissue was obtained from 45 otherwise healthy male children who underwent elective surgery for hernia repairs or orchidopexy. The children were divided into overweight/obese (n = 17) or normal weight groups (n = 28) depending on their body mass index (BMI) z-score. Serum was obtained for glucose, testosterone, triglyceride, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) measurements. Sections of adipose tissue were stained with hematoxylin and eosin to determine the adipocytes’ surface area, and Masson’s trichrome stain was used to detect the adipocytes’ collagen content. Immunohistochemistry for CD163+ cells was also performed. The results showed that male children in the overweight group had higher serum triglyceride levels, greater adipocyte surface area and collagen content in their subcutaneous adipose tissue, more crown-like structures in fat tissues, and more CD163+ cells in their visceral adipose tissue than males in the normal weight group. In conclusion, in male children, obesity can lead to the hypertrophy of adipocytes, increased collagen deposition in subcutaneous adipose tissues, and changes in the polarization and accumulation of macrophages.

Amyrins from Protium heptaphyllum Reduce High-Fat Diet-Induced Obesity in Mice via Modulation of Enzymatic, Hormonal And Inflammatory Responses.

Obesity remains a global problem. In search of phytochemicals that have antiobesity potential, this study evaluated α,β-amyrin, a triterpenoid mixture from Protium heptaphyllum, on high-fat diet-induced obesity in mice. Groups of mice (n = 8) were fed a normal diet or a high-fat diet, and were orally treated or not treated with either α,β-amyrin (10 or 20 mg/kg) or sibutramine (10 mg/kg) for 15 weeks. Variables measured at termination were body weight, visceral fat accumulation, adipocyte surface area, peroxisome proliferator-activated receptor gamma, and lipoprotein lipase expressions in adipose tissue, the levels of plasma glucose and insulin, the satiety hormones ghrelin and leptin, the digestive enzymes amylase and lipase, and the inflammatory mediators TNF-α, interleukin-6, and MCP-1. Results showed that α,β-amyrin treatment resulted in lower high-fat diet-induced increases in body weight, visceral fat content, adipocyte surface area, peroxisome proliferator-activated receptor gamma, and lipoprotein lipase expressions, and blood glucose and insulin levels. Additionally, the markedly elevated leptin and decreased ghrelin levels seen in the high-fat diet-fed control mice were significantly modulated by α,β-amyrin treatment. Furthermore, α,β-amyrin decreased serum TNF-α and MCP-1. These results suggest that α,β-amyrin could be beneficial in reducing high-fat diet-induced obesity and associated disorders via modulation of enzymatic, hormonal, and inflammatory responses.

An activated sympathetic nervous system affects white adipocyte differentiation and lipolysis in a rat model of Parkinson's disease.

Weight loss is an important nonmotor symptom associated with Parkinson's disease (PD). However, the cellular factors responsible for PD-induced weight loss remain unclear. Because the sympathetic nervous system plays an important role in lipid metabolism and fat cell differentiation, this study investigates whether PD-induced changes to this system are associated with weight loss in a rat model of PD. Body weight and food intake were measured in control and PD-model rats. After 10 weeks, retroperitoneal white adipose tissues (RWAT) were removed and weighed. Markers of the sympathetic nervous system were measured in the brainstem dorsal medulla and RWAT. Free fat acids (FFA), triglycerides (TG), adipocyte differentiation-related genes, and lipolysis-related molecules in the RWAT and serum were analyzed. Differences in body weight and food intake were insignificant in PD-model rats and control rats; however, relative RWAT weight and adipocyte surface area were significantly reduced in the PD group. Changes in markers of the sympathetic nervous system were observed in the brainstem dorsal medulla and RWAT of PD rats. Decreased mRNA expression levels of genes involved in adipocyte differentiation, decreased TG levels in RWAT, increased FFA in RWAT, and increased lipolysis-related molecules in RWAT and serum FFA were observed in PD rats. This study demonstrates that degenerated dopaminergic neurons in the nigrostriatal system correlate with increases in sympathetic nervous system function, resulting in lipolysis and inhibition of fat cell differentiation. These factors ultimately result in the decrease of RWAT in PD-model rats.

Expression of the human apoE2 isoform in adipocytes: altered cellular processing and impaired adipocyte lipogenesis

Expression of apoE in adipocytes has been shown to have an important role in modulating adipocyte triglyceride (TG) metabolism and gene expression that is independent of circulating and extracellular apoE. The impact of adipocyte expression of common human apoE isoforms was evaluated using adipocytes harvested from human apoE2, -3, and -4 knock-in mice. Expression of the apoE2 isoform was associated with an increase in adipocyte apoE gene expression and apoE synthesis. Newly synthesized apoE2 was unstable in adipocytes and demonstrated increased degradation and decreased secretion. ApoE2-expressing mice were hyperlipidemic, and had increased size of gonadal fat pads and of adipocytes, compared with apoE3 mice. In isolated cells, however, expression of the apoE2 isoform produced defective lipogenesis and increased TG hydrolysis. Incubation of adipose tissue with apoE3-containing TG-rich lipoproteins resulted in a significant increase in TG in adipose tissue from apoE3 and -E4 mice, but not apoE2 mice. Reduced capacity to internalize FFA as lipogenic substrate contributed to defective lipogenesis. Newly synthesized apoE2 is unstable in adipocytes and results in decreased adipocyte TG synthesis and defective FA uptake. These changes recapitulate those observed in apoE knockout adipocytes and have implications for understanding metabolic disturbances in humans expressing the E2 isoform.

Resistance to the antilipolytic effect of insulin in adipocytes of African-American compared to Caucasian postmenopausal women

High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant. We assessed possible depot and race difference in the antilipolytic effect of insulin in adipocytes isolated from abdominal (Abd) and gluteal (Glt) subcutaneous (sc) adipose tissue of overweight, postmenopausal AA and Caucasian (C) women. Percent body fat, fasting insulin, visceral adiposity, and adipocyte size was higher in AA women. Disinhibited lipolysis (presence of adenosine deaminase) per unit adipocyte surface area was similar in Abd and Glt and in AA and C. However, rates of 'basal' [submaximal phenylisopropyl adenosine (PIA)-suppressed] and insulin-suppressed lipolysis were higher in Abd of AA compared with C women even after adjustment for percent fat and visceral fat area. The race difference in rates of PIA- and insulin-suppressed lipolysis in AA were correlated with their hyperinsulinemia, but AA race, independent of fasting insulin, was associated with lower responsiveness (percent suppression) to submaximal insulin concentrations, although sensitivity (ED50) was not affected. Overall, these data are consistent with the hypothesis that decreased responsiveness of Abd adipocytes to antilipolytic effectors may contribute to higher FA availability and thereby to racial differences in insulin resistance.

Deletion of Tumor Necrosis Factor-α Receptor 1 (TNFR1) Protects against Diet-induced Obesity by Means of Increased Thermogenesis

In diet-induced obesity, hypothalamic and systemic inflammatory factors trigger intracellular mechanisms that lead to resistance to the main adipostatic hormones, leptin and insulin. Tumor necrosis factor-alpha (TNF-alpha) is one of the main inflammatory factors produced during this process and its mechanistic role as an inducer of leptin and insulin resistance has been widely investigated. Most of TNF-alpha inflammatory signals are delivered by TNF receptor 1 (R1); however, the role played by this receptor in the context of obesity-associated inflammation is not completely known. Here, we show that TNFR1 knock-out (TNFR1 KO) mice are protected from diet-induced obesity due to increased thermogenesis. Under standard rodent chow or a high-fat diet, TNFR1 KO gain significantly less body mass despite increased caloric intake. Visceral adiposity and mean adipocyte diameter are reduced and blood concentrations of insulin and leptin are lower. Protection from hypothalamic leptin resistance is evidenced by increased leptin-induced suppression of food intake and preserved activation of leptin signal transduction through JAK2, STAT3, and FOXO1. Under the high-fat diet, TNFR1 KO mice present a significantly increased expression of the thermogenesis-related neurotransmitter, TRH. Further evidence of increased thermogenesis includes increased O(2) consumption in respirometry measurements, increased expressions of UCP1 and UCP3 in brown adipose tissue and skeletal muscle, respectively, and increased O(2) consumption by isolated skeletal muscle fiber mitochondria. This demonstrates that TNF-alpha signaling through TNFR1 is an important mechanism involved in obesity-associated defective thermogenesis.

Behavioral patterns related to social interaction with peers in developing marmosets

The aim of the present study was to investigate the GLUT4 protein expression during the development of obesity in monosodium glutamate- (MSG) treated mice. Control (C) and neonatally MSG-treated 2-month-old (2-mo), 4-month-old (4-mo) and 7-month-old (7-mo) mice were analyzed. Anthropometric data, basal glycemia and insulinemia were measured; and the GLUT4 protein was assessed by Western blotting in white adipose tissue (WAT), skeletal muscle gastrocnemius (SM) and heart (H). Compared to age-matched C mice, the 2-mo and 4-mo MSG mice were already obese, but metabolically they showed increased or preserved whole-body insulin sensitivity, respectively. At these ages they showed unchanged total GLUT4 content in SM and H. However, in plasma membrane fraction from WAT, the MSG showed increased GLUT4 content at both 2- (by 60%) and 4-month (by 45%) of age. When the GLUT4 protein was expressed by unit of adipocyte surface area the protein amount was increased by 36 and 220% in 2-mo and 4-mo MSG mice, respectively. At 7 months of age, obesity was fully established in MSG mice, showing a strongly insulin resistant condition. Additionally, in the 7-mo MSG-mice the GLUT4 protein was reduced in SM (by 40%), H (by 28%), PM and M fractions of WAT (by ∼70%), and PM expressed by unit of adipocyte surface area (by 92%). The data demonstrate that early, during the accelerated development of obesity in MSG-treated mice, the GLUT4 content was increased in WAT, and that may play a key role in the development of obesity. Later on, when obesity is fully established, the GLUT4 protein was reduced in SM, heart and WAT, and that may be involved in the insulin resistance present in this condition.

Long-chain fatty acid uptake is upregulated in omental adipocytes from patients undergoing bariatric surgery for obesity

To determine the impact of obesity on adipocyte cell size and long-chain fatty acid (LCFA) uptake kinetics in human subjects undergoing laparoscopic abdominal surgery. A total of 10 obese patients (BMI 49.8+/-11.9 (s.d.) kg/m(2)) undergoing laparoscopic bariatric surgery, and 10 nonobese subjects (BMI 24.2+/-2.3 kg/m(2)) undergoing other clinically indicated laparoscopic abdominal surgical procedures. Cell size distribution and [(3)H]oleic acid uptake kinetics were studied in adipocytes isolated from omental fat biopsies obtained during surgery. Adipocyte surface area (SA) was calculated from the measured cell diameters. Plasma leptin and insulin concentrations were measured by RIA in fasting blood samples obtained on the morning of surgery. The mean SA of obese adipocytes (41 508+/-5381 mu(2)/cell) was increased 2.4-fold compared to that of nonobese adipocytes (16 928+/-6529 mu(2)/cell; P<0.01). LCFA uptake in each group was the sum of saturable and nonsaturable components. Both the V(max) of the saturable component (21.3+/-6.3 vs 5.1+/-1.9 pmol/s/50,000 cells) and the rate constant k of the nonsaturable component (0.015+/-0.002 vs 0.0066+/-0.0023 ml/s/50 000 cells) were increased (P<0.001) in obese adipocytes compared with nonobese controls. When expressed relative to cell size, V(max)/mu(2) SA was greater in obese than nonobese adipocytes (P<0.05), whereas k/mu(2) SA did not differ between the groups. The data support the concepts that (1) adipocyte LCFA uptake consists of distinct facilitated (saturable) and diffusive processes; (2) increased saturable LCFA uptake in obese adipocytes is not simply a consequence of increased cell size, but rather reflects upregulation of a facilitated transport process; and (3) the permeability of adipocyte plasma membranes to LCFA is not appreciably altered by obesity, and increased nonsaturable uptake in obese adipocytes principally reflects an increase in cell SA. Regulation of saturable LCFA uptake by adipocytes may be an important control point for body adiposity.

GLUT4 protein is differently modulated during development of obesity in monosodium glutamate-treated mice

The aim of the present study was to investigate the GLUT4 protein expression during the development of obesity in monosodium glutamate- (MSG) treated mice. Control (C) and neonatally MSG-treated 2-month-old (2-mo), 4-month-old (4-mo) and 7-month-old (7-mo) mice were analyzed. Anthropometric data, basal glycemia and insulinemia were measured; and the GLUT4 protein was assessed by Western blotting in white adipose tissue (WAT), skeletal muscle gastrocnemius (SM) and heart (H). Compared to age-matched C mice, the 2-mo and 4-mo MSG mice were already obese, but metabolically they showed increased or preserved whole-body insulin sensitivity, respectively. At these ages they showed unchanged total GLUT4 content in SM and H. However, in plasma membrane fraction from WAT, the MSG showed increased GLUT4 content at both 2- (by 60%) and 4-month (by 45%) of age. When the GLUT4 protein was expressed by unit of adipocyte surface area the protein amount was increased by 36 and 220% in 2-mo and 4-mo MSG mice, respectively. At 7 months of age, obesity was fully established in MSG mice, showing a strongly insulin resistant condition. Additionally, in the 7-mo MSG-mice the GLUT4 protein was reduced in SM (by 40%), H (by 28%), PM and M fractions of WAT (by ∼70%), and PM expressed by unit of adipocyte surface area (by 92%). The data demonstrate that early, during the accelerated development of obesity in MSG-treated mice, the GLUT4 content was increased in WAT, and that may play a key role in the development of obesity. Later on, when obesity is fully established, the GLUT4 protein was reduced in SM, heart and WAT, and that may be involved in the insulin resistance present in this condition.

Characterization of cyclic AMP efflux from swine adipocytes in vitro.

A variety of cell types transport cyclic AMP (cAMP) to the extracellular fluid; the purpose of this study was to determine if and how this process occurs in adipocytes. Adipocytes were isolated from 3-month-old swine and incubated with stimulators of adenylate cyclase for 2 to 120 minutes to promote cAMP synthesis and efflux. Efflux was characterized in the presence of agents that inhibit ATP production, anion transport, intracellular cAMP metabolism, and extracellular cAMP metabolism. Extracellular cAMP was measured by enzyme immunoassay, then corrected for cell lysis by measuring lactate dehydrogenase release. cAMP efflux averaged 24.7 fmol/min/cm2 adipocyte surface area, was linear for 2 hours, and was proportional to adipocyte surface area (r=0.94, p<0.05). Efflux was reduced by approximately 35% in cells incubated with 1 microM antimycin, an inhibitor of ATP synthesis (p<0.05), and by approximately 55% in cells incubated with 2 mM probenecid, an anion-specific transport blocker (p<0.05). Extracellular cAMP levels more than doubled by the addition of 1 microM 1,3-dipropyl-8-p-sulfophenylxanthine, a purported inhibitor of extracellular phosphodiesterase. Our data demonstrate that cAMP is transported from swine adipocytes by an energy-dependent anion transporter and can be metabolized extracellularly. Future studies will evaluate extracellular cAMP as a potential source of extracellular adenosine, a potent inhibitor of adipocyte lipolysis.

Beta-adrenergic receptors in porcine adipocyte membranes: modification by animal age, depot site, and dietary protein deficiency.

Adipocyte lipid metabolism is primarily regulated by insulin and the catecholamines norepinephrine and epinephrine. Stimulation of the beta-adrenergic receptors (beta-AR) by catecholamines causes an increase in the rates of adipocyte lipid degradation and a decrease in the rates of lipid synthesis. These catabolic effects are in opposition to insulin, which causes net anabolic effects. Because most of the postnatal development of adipose tissue mass in pigs results from hypertrophy of adipocytes (rapid in first few weeks of life) caused by increased net synthesis of triacylglycerol, there is interest in the modulation of beta-AR in adipocytes of growing pigs. The beta-AR are characterized by measuring ligand binding to the receptor to ascertain the affinity of the ligand for the receptor and the receptor number. We found the affinity of the receptor did not vary with animal age (10, 28, and 75 d), with adipose tissue depot site, or in adipocytes of protein-deficient pigs. The beta-AR in obese pigs tended to have greater affinity than those in crossbred pigs of the same age and weight. The beta-AR number was not different when expressed per milligram of adipocyte membrane protein in pigs of different age, in obesity, in different adipose tissue depots, or during protein deficiency. The number expressed per cell or per unit adipocyte surface area did not differ between depots or during protein deficiency. The number per cell tended to be greater in the larger cells from 75-d-old pigs than in the smaller cells from 10- and 28-d pigs. It was greatest in obese pigs with the largest adipocytes. Under the various experimental conditions (age, obesity, depot, protein deficiency), the membrane fatty acid composition was greatly different, but in most cases there was no modulation of beta-AR affinity.

Prostaglandin E 2 action and binding in human adipocytes: Effects of sex, age, and obesity

The antilipolytic effect of prostaglandin E 2 (PGE 2) was studied in subcutaneous human adipocytes. The influence of sex, age, and obesity on the PGE 2 effect was investigated. The antilipolytic effects of PGE 2 were related to the PGE 2 binding data obtained in the same adipocytes. The maximal antilipolytic action of PGE 2 was slightly reduced in adipocytes in males compared with females (maximal inhibition 86% v 97%, P > .05). The PGE 2 binding was similar in adipocytes in females and males. The antilipolytic effect of PGE 2 and the PGE 2 binding was similar when young females were compared with older females. However, the antilipolytic effect of PGE 2 was significantly reduced in obese compared with nonobese subjects. If lipolysis was only stimulated by adenosine deaminase, the sensitivity of PGE 2 was reduced in obesity (IC 50, 1.45 nmol/L v 0.47 nmol/L, P < .01), but the maximal antilipolytic effect of PGE 2 in the two groups was similar, with an inhibitory effect of 95% to 98%. If lipolysis was stimulated by both adenosine deaminase and theophylline (2 mmol/L), it was especially the maximal antilipolytic effect of PGE 2 that was impaired in adipocytes from obese subjects (lipolysis was maximally inhibited by 61% v 92%, P < .01). When the PGE 2 binding was expressed in relation to adipocyte surface area, the total binding capacity (B max) was reduced in adipocytes in obese subjects from 26.5 to 17.9 fmol 100 cm 2 ( P < .05). In contrast to PGE 2, the antilipolytic effect of the α 2-adrenergic agonist clonidine was similar between the two groups, and in accordance with that finding, the α 2-receptor binding to adipocytes was also similar in the two groups. Thus, the reduced antilipolytic effect of PGE 2 does not seem to involve a more general impairment of the antilipolytic pathways in adipocytes from obese subjects.

Influence of obesity on the antilipolytic effect of insulin in isolated human fat cells obtained before and after glucose ingestion.

The antilipolytic effect of insulin was studied in 9 obese and 10 age- and sex-matched subjects of normal weight. Isolated fat cells were taken before and 1 h after an 100 g oral glucose load. Insulin inhibition of basal and isoprenaline-induced rates of lipolysis were determined by using a sensitive bioluminescent glycerol assay. When compared with the controls, the obese group showed a lower glucose tolerance, a higher insulin secretion, and a lower specific insulin receptor binding per adipocyte surface area, which would suggest an insulin-resistant state. Before oral glucose, however, the sensitivity of the antilipolytic effect of insulin was enhanced 10-fold in obesity (P less than 0.01), but the maximum antilipolytic effect was not altered. Glucose ingestion induced a 10-25-fold increase in insulin sensitivity (P less than 0.01) and a 10% but not significant increase in specific adipocyte insulin receptor binding in the nonobese group. In the obese group, however, neither the insulin binding nor the antilipolytic effect of the hormone was increased by oral glucose. After oral glucose, insulin sensitivity was similar in the two groups. The concentration of the hormone which produced a half maximum effect was about 1 microU/ml. Similar results were obtained with insulin inhibition of basal and isoprenaline-stimulated glycerol release. It is concluded that, after an overnight fast, the sensitivity of the antilipolytic effect of insulin is markedly enhanced in adipocytes of "insulin-glucose resistant" obese subjects, presumably because of alterations at postreceptor levels of insulin action. In obesity, the antilipolytic effect of insulin seems normal after glucose ingestion. Furthermore, in adipocytes of subjects of normal weight, oral glucose rapidly stimulates the sensitivity of the antilipolytic effect of insulin, apparently because of changes at postreceptor sites. This short-term regulation of insulin action following the ingestion of glucose does not seem to be present in obesity.

Thyroid-hormone modulation of the number of β-adrenergic receptors in rat fat-cell membranes

Adipocytes from thyroidectomized rats contain 3 times less [3H]dihydroalprenolol-binding sites (beta-adrenergic receptors) than adipocytes from euthyroid animals. This alteration is not solely due to cell-size differences, but also to a thyroidectomy-induced defect in beta-adrenergic receptor density per adipocyte surface area, a defect that is furthermore corrected by tri-iodothyronine treatment.

Adipose-tissue lipoprotein lipase activity and cellularity in the genetically obese Zucker rat (fa-fa).

The lipoprotein lipase activity per adipocyte was increased in the genetically obese rat (fa/fa). However, there was no difference between obese and lean animals when the enzyme activities were related to adipocyte surface area. The possible implications of the findings are discussed.