Parathyroid hormone-induced lipolysis in human adipose tissue

Relative lipolytic activity of human parathyroid hormone-(1-34) (hPTH-(1-34], hPTH-(3-34), desamino-Ser1-hPTH-(1-34), and rat PTH-(1-34) was compared in human subcutaneous adipose tissues in vitro. Human PTH-(1-34), rat PTH-(1-34), and desamino-Ser1-hPTH-(1-34) stimulated in vitro lipolysis significantly above basal level at the concentration of 10(-6) M. Average increments of lipolytic rate were 2.39, 1.82, and 0.87 mumol/g per 2 hr, respectively, being significantly different among the three groups. On the other hand, hPTH-(3-34)-induced lipolytic rate was 0.83 +/- 0.18 mumol/g per 2 hr, not significantly different from the basal level (0.71 +/- 0.20 mumol/g per 2 hr). The effect of hPTH-(3-34) on glycerol release stimulated by hPTH-(1-34), isoproterenol, or forskolin was subsequently investigated. Human PTH-(3-34) produced a dose-dependent inhibition of hPTH-(1-34)-stimulated lipolysis. In contrast, isoproterenol- and forskolin-induced lipolytic rates were not influenced by hPTH-(3-34). The effect of propranolol on hPTH-(1-34)- or isoproterenol-induced lipolysis was also studied. Propranolol dose-dependently inhibited isoproterenol-induced lipolysis but had no effect on lipolysis stimulated by hPTH-(1-34). These results suggest that the amino acids at positions 1 (serine) and 2 (valine) of PTH are critical for the stimulation of lipolysis in human adipose tissue. Human PTH-(1-34) causes lipolysis after binding to receptors distinct from beta-adrenergic receptors of fat cells and possibly hPTH-(3-34) inhibits hPTH-(1-34)-stimulated lipolysis by competing at the level of PTH receptor.     

Regional and gender variations in adipose tissue lipolysis in response to weight loss.

Catecholamine-induced lipolysis was investigated in 32 obese subjects (14 men and 18 premenopausal women), aged 36-50 years, whose body mass index ranged from 30 to 42 kg/m(2). Isolated subcutaneous (subc) abdominal and femoral adipocytes were studied before and after a 15-week weight reducing program, during which mean body weight loss averaged 9 vs. 10 kg in women and men, respectively (P < 0.0001). Participants were re-examined when they were weight-stable. Fat cell weight decreased by about 15;-20% in both depots (P values ranging from 0.01 to 0.05). Epinephrine (mixed alpha2-/beta-adrenoceptor (AR) agonist) induced antilipolysis at low concentrations and a net lipolytic response at higher doses, irrespective of subjects' fatness and anatomic location of fat. Basal lipolysis, maximal lipolytic responses to isoprenaline (beta-AR agonist), dobutamine and procaterol (beta1- and beta2-AR agonists, respectively) as well as maximal antilipolytic effects of epinephrine or UK-14304 (alpha2-AR agonist) were similar before and after weight reduction. However, both beta- and beta2-AR lipolytic sensitivities and the beta-AR density were increased in both genders after weight reduction, this effect being more marked in subc abdominal than in femoral adipocytes (P values ranging from 0.001 to 0.05). The alpha2-AR antilipolytic sensitivity was reduced in adipose cells from both regions in women, but only in subc abdominal adipocytes in men (P < 0.05), although the alpha2-AR density remained unchanged after weight reduction. In conclusion, a moderate weight loss leads to a higher adipose cell lipolytic efficiency which is associated with changes at receptor levels (mainly an increased beta2- and a decreased alpha2-AR sensitivities), in both genders.     

Growth and lipolysis of rat adipose tissue: effect of age, body weight, and food intake

The purpose of the present work was to study age- and weight-controlled rats to determine which is the primary factor in reducing the lipolytic response of free fat cells and which has the greater effect on the ratio of fat cells to nonfat cells in adipose tissue. The method for estimating fat cell and nonfat cell numbers is based on the analysis of adipose tissue and fat cell DNA and lipid. In adequately fed rats, epididymal adipocyte hyperplasia is complete between 9 and 14 wk of age. Chronic underfeeding delays, but does not eliminate, normal fat cell hyperplasia and is accompanied by a net loss in the nonfat cell population. During 9-14 wk of age, rat epididymal adipose tissue enlarges mainly through adipocyte hypertrophy. Total fat cells from the epididymal adipose tissue of control rats represent only 20-23% of the total cell population. Chronic underfeeding increases the percentage of fat cells in the fat pad from 23 to 28%. Noradrenaline-stimulated lipolysis is proportional to fat cell numbers but is inhibited when fat cell lipid increases to over 80% of fat pad wet weight. Rat age is apparently not primarily responsible for the decreased noradrenaline-stimulated lipolysis in fat cells of 350-g rats in vitro.     

The role of neutral lipases in human adipose tissue lipolysis

PURPOSE OF REVIEW: The aim of this article is to describe the relative roles of hormone sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis. RECENT FINDINGS: Until recently, only hormone sensitive lipase was considered important for the regulation of lipolysis within fat cells. Recent rodent studies have suggested that adipose triglyceride lipase may, however, be more important. The few human adipose triglyceride lipase studies that have been published point to species differences between humans and rodents. Selective inhibition of hormone sensitive lipase in human fat cells completely counteracts hormone-activated lipolysis, though there is a considerable (>50%) residual nonhormonal (basal) lipolysis. In rodents, adipose triglyceride lipase enzyme activity is stimulated by a cofactor termed CGI-58. In the absence of CGI-58, lipase activity in fat cells is much higher for hormone sensitive lipase than adipose triglyceride lipase. Hormone sensitive lipase expression is regulated by obesity and body weight reduction (decreased and increased, respectively), but this is not the case for adipose triglyceride lipase. A role of adipose triglyceride lipase in human lipolysis is suggested by studies of gene polymorphisms. SUMMARY: Two lipases the 'old' hormone sensitive lipase and the 'new' adipose triglyceride lipase are of importance for the regulation of lipolysis in rodent fat cells. In humans, adipose triglyceride lipase seems essential for maintaining basal lipolytic activity, while hormone sensitive lipase is the enzyme most responsive to stimulated lipolysis.     

Fatty acid binding protein expression in different human adipose tissue depots in relation to rates of lipolysis and insulin concentration in obese individuals

Two fatty acid binding proteins (FABPs) are expressed in adipose tissue, adipocyte lipid binding protein (ALBP) and keratinocyte lipid binding protein (KLBP). This study investigated FABP expression in visceral and subcutaneous human adipose tissue depots and associations with lipolytic differences between the depots and circulating insulin concentrations. ALBP and KLBP (protein and RNA) were quantified in subcutaneous and omental adipose tissue from obese individuals and expressed relative to actin. ALBP RNA and protein expression was significantly higher in subcutaneous compared to omental adipose tissue (both p < 0.05), whereas KLBP RNA and protein expression was no different between the two sites. There were significant inverse correlations between serum insulin concentrations and the ALBP/KLBP RNA ratio in both subcutaneous and omental adipose tissue (both p < 0.02). Basal rates of glycerol and fatty acid release measured in adipocytes isolated from subcutaneous and omental adipose tissue were significantly higher in the former (p 0.02). Therefore the relative ALBP/KLBP content of human adipose tissue is different in different adipose tissue depots and at the RNA level is related to the circulating insulin concentration, at least in obese subjects. The higher rates of basal lipolysis in adipocytes isolated from subcutaneous compared to omental adipose tissue might be related to the increased ALBP content of the former. Therefore adipose tissue FABPs are interesting candidates for investigation to further our understanding of the insulin resistance syndrome and regulation of lipolysis.     

Catecholamine effects on lipolysis and blood flow in human abdominal and femoral adipose tissue

With the use ofthe microdialysis method, the present study, performed on young,healthy, nonobese subjects of both genders, compares the effects oflocally infused catecholamines on glycerol concentration and blood flowin abdominal (Abd) and femoral (Fem) adipose tissue. Physiologicalactivation of the sympathetic nervous system through active tilt wasalso investigated. In both genders, extracellular glycerolconcentration was higher in Fem than in Abd adipose tissue. Local bloodflow was lower in Fem than in Abd adipose tissue. Isoproterenolperfusion increased extracellular glycerol levels, but no differenceswere found by gender or fat-deposit site. Isoproterenolinduced a greater increase in local blood flow in Fem adipose tissue inboth genders. Epinephrine and norepinephrine perfusion increasedextracellular glycerol and reduced blood flow. No major differenceswere found according to gender and fat-deposit site. Active tiltincreased plasma glycerol, free fatty acid, norepinephrine levels, andextracellular glycerol concentration to the same extent whatever thegender and fat deposit. Thus, Fem adipose tissue is characterized by ahigher extracellular glycerol concentration and a lower blood flow thanis Abd tissue in men and women. In these tissues, in situ lipolysis andlocal blood flow were similar in response to adrenergic stimulation.

     

Adrenergic control of lipolysis in swine adipose tissue

Most potential adrenergic compounds did not stimulate lipolysis in swine adipose tissue slices. Most of the sympatholytic agents antagonized lipolysis. Most beta 1- and beta 2-adrenergic agonists were not active but many were active with rat adipose tissue. Catecholamines (epinephrine, norepinephrine and isoproterenol), the resorcinol containing beta 2-agonists (terbutaline, metaproterenol and fenoterol) and the beta 1-agonist, dobutamine were active. The beta 1-antagonists were generally more potent and efficacious than the beta 2-antagonists. The swine adipose tissue adrenoceptor was not readily classified as either beta 1- or beta 2-specific.     

Brain insulin controls adipose tissue lipolysis and lipogenesis

White adipose tissue (WAT) dysfunction plays a key role in the pathogenesis of type 2 diabetes (DM2). Unrestrained WAT lipolysis results in increased fatty acid release, leading to insulin resistance and lipotoxicity, while impaired de novo lipogenesis in WAT decreases the synthesis of insulin-sensitizing fatty acid species like palmitoleate. Here, we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague-Dawley rats increases WAT lipogenic protein expression, inactivates hormone-sensitive lipase (Hsl), and suppresses lipolysis. Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and, in particular, hypothalamic insulin action play a pivotal role in WAT functionality.     

Endoplasmic reticulum stress in adipose tissue augments lipolysis

The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca²⁺ homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 24–48 hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs.