The involvement of glucocorticoids (GC) in the development of diet-induced obesity and in the concomitant adaptations of triglyceride (TG)-rich lipoprotein metabolism were examined. Rats were fed either rodent chow, which maintains a low lipid flux, or a diet high in sucrose and fat (HSF) that increases lipid flux, leading to metabolic perturbations similar to those that define the plurimetabolic syndrome in humans. The GC status was manipulated through adrenalectomy (ADX) and corticosterone (Cort) replacement. Compared with chow, the HSF diet increased energy intake (17%) and whole body (8%) and adipose tissue (80%) weights. The HSF diet also increased the acute postprandial rise in plasma insulin (4-fold) and TG (3-fold), fasting liver TG content (3-fold), triglyceridemia (54%), and adipose tissue lipoprotein lipase (LPL) activity (2-fold). ADX decreased energy intake and whole body and adipose tissue weights in both dietary cohorts, but more so in HSF-fed than in chow-fed animals. These ADX-induced effects were totally prevented by Cort replacement in rats fed chow, but only partially so in those fed the HSF diet in proportion to the degree of restoration of energy intake. In the chow-fed cohort, the above indexes of TG metabolism remained unaffected by the Cort status, whereas in the HSF-fed cohort, these variables were decreased by ADX to levels of chow-fed animals. Cort replacement in the HSF-fed animals restored indexes of TG metabolism to intact levels and reestablished the diet-related differences observed in intact animals. These findings indicate that GC modulate fasting TG metabolism only minimally when a diet that maintains a low lipid flux is fed. In contrast, their presence is a necessary condition for the development of diet-induced obesity and the concomitant alterations in insulin sensitivity and TG-rich lipoprotein metabolism.

This study aimed to identify the metabolic steps involved in the acute hypotriglyceridemia brought about by increased energy expenditure (cold exposure) and to assess the causative involvement of some determinants of triglyceride (TG) metabolism as well as that of the β-adrenergic pathway. Rats were kept at 24°C or exposed to 10°C for 3 h after acute administration of the β-adrenergic antagonist propranolol (Prop) or vehicle. Cold exposure increased the rate of TG secretion (Triton WR1339 method) into the circulation by 50% ( P < 0.0005), an effect that was blunted by Prop. The cold-induced increase in TG secretion was closely related to changes in circulating nonesterified fatty acid levels, but not with serum insulin concentrations. Despite an increase in TG secretion, serum TG levels after acute cold exposure fell to 50% ( P < 0.002) of those measured at 24°C, indicating that the lowering of serum TG was entirely due to an increase in their rate of intravascular hydrolysis. This was confirmed by observing a 70% increase ( P < 0.002) in the rate of clearance of an exogenous TG emulsion in cold-exposed rats compared with those kept in the warm. Prop treatment before cold exposure decreased (∼30%, P < 0.005) the cold-induced stimulation of TG hydrolysis. The increased TG clearance rate in cold-exposed animals occurred in the absence of any change in the intravascular availability of lipoprotein lipase (LPL). In contrast, the activity of LPL displayed a tissue-specific response to cold exposure, being reduced by one-half in white adipose tissue ( P < 0.0005) and increased in brown adipose tissue (130%, P < 0.0001) and the heart (50%, P < 0.001). These findings show that, in the postprandial state, an acute increase in energy expenditure induced by cold exposure results in a lowering of serum TG entirely due to an increase in their rate of intravascular hydrolysis and that serum TGs are lowered despite an increase in the rate of TG secretion into the circulation. More efficient TG hydrolysis occurs independently of the intravascular availability of LPL. The study further shows that the effects of cold exposure on serum TG concentration and their rates of secretion and clearance are in large part mediated by the β-adrenergic pathway.

This study aimed to dissociate the peripheral effects of adrenalectomy (ADX) on triglyceride (TG) metabolism from those it exerts centrally on energy intake and to determine the impact of diet composition therein. Rats were fed either rodent chow or a diet high in sucrose and fat (HSF) and were adrenalectomized or left intact and pair fed to the ADX animals. Liver TG content, an index of hepatic TG production, was not affected by ADX, but was increased twofold by the HSF diet. ADX decreased the rate of hepatic TG secretion by 41% in chow-fed but not in HSF-fed animals. Triglyceridemia and postheparin plasma lipase activities remained largely unchanged by treatments. ADX decreased insulinemia fivefold in chow-fed rats, but less so in HSF-fed animals. Likewise, subcutaneous and visceral adipose depots were 40-60% smaller in ADX than in intact pair-fed rats given chow, but the effect of ADX was dampened by consumption of the HSF diet. Although smaller, adipose tissues of ADX rats maintained a higher activity of lipoprotein lipase (LPL) than those of intact pair-fed rats, whereas muscle LPL was decreased. The study confirms that in the presence of reduced energy intake, corticosterone contributes to the maintenance of adipose stores and that the consequences of its absence tend to be attenuated when a high-energy diet is fed. The study further shows that, contrary to ad libitum feeding conditions, most determinants of TG metabolism, such as hepatic TG stores, triglyceridemia, postheparin plasma LPL, and adipose tissue LPL, are minimally affected by glucocorticoids when consumption of a high-energy diet is restricted, suggesting that glucocorticoids affect TG metabolism mostly indirectly through their central action on ingestive behavior.

OBJECTIVE:To characterize the developmental changes in adipose and muscle lipoprotein lipase (LPL) activity in the atherosclerosis-prone JCR:LA-corpulent rat, and to test the hypothesis that tissue-specific abnormalities in LPL activity precede the establishment of obesity. DESIGN: Lean ( þ =?) and obese cp=cp male JCR:LA rats were studied at 4, 5 and 8 weeks of age, that is at the onset of obesity, and at a time when obesity is well established. Assessment was made of plasma variables related to glucose and lipid metabolism and of LPL activity in several adipose depots, skeletal muscles and the heart. RESULTS: At week 4, body weights were identical in both genotypes and began to diverge at week 5. Eight-week-old cp=cp rats weighed 35% more than their lean counterparts. Perirenal and epididymal adipose depot weights were also identical in both genotypes at week 4 and began to increase in cp=cp rats at week 5, whereas the subcutaneous depot of 4-week-old cp=cp rats was slightly enlarged. At week 4, the cp=cp rats were hyperinsulinemic (5-fold), hyperleptinemic (30-fold) and hypertriglyceridemic (3-fold) compared to their lean counterparts, and their liver contained twice as much triglyceride. The 4-week-old cp=cp rats displayed 2 -7-fold higher LPL specific activity in the various adipose depots compared to lean rats, and enzyme activity remained higher in obese than in lean rats at all subsequent ages. In contrast, LPL activity in the vastus lateralis, gastrocnemius and heart muscles of 4-week-old obese rats was approximately half that observed in lean animals. CONCLUSION: Profound, persistent alterations in the tissue-specific modulation of LPL activity are established in the JCR:LA cp=cp rat prior to the development of frank obesity. The increase in adipose tissue LPL activity and its decrease in muscle tissues are likely to be related to the concomitant alterations in insulinemia and triglyceridemia, respectively. The pre-obesity, tissuespecific alterations in LPL activity may be considered as an integrated adaptation to increased lipid flux aimed at driving lipids toward storage sites and limiting their uptake by triglyceride-laden muscles.