The regulation of total body fat: lessons learned from lipectomy studies.

Surgical removal of body fat (partial lipectomy) is a means of directly reducing fat such that metabolic and behavioral responses can be readily attributed to the lipid deficit. If total body fat is regulated, then lipectomy should trigger compensatory increases in nonexcised white adipose tissue (WAT) mass and/or regrowth at excision sites. Many species, including laboratory rats and mice, show lipectomy-induced compensatory recovery of body fat. Those animals exhibiting naturally occurring annual adiposity cycles, such as ground squirrels and hamsters, do so most impressively reaching seasonally appropriate body fat levels indistinguishable from controls. Reparation of the lipid deficit occurs without an increase in food intake, and generally through enlargement of non-excised WAT mass, rather than regrowth of excised WAT. A body fat regulatory system involving humoral and sensory neural inputs to the brain as well as sympathetic neural outputs from brain to adipose tissue is presented. Collectively, the lipectomy model appears useful for testing mechanisms controlling adiposity, or individual depot growth, and offers insight into how lipid stores fluctuate naturally.

Temporal changes in fat pad mass and cellularity after lipectomy in Siberian hamsters.

Long-day-housed Siberian hamsters show increases in the mass of nonexcised white adipose tissue (WAT) 12 weeks after bilateral removal (x) of epididymal WAT (EWAT). Although EWAT shows no significant regeneration, surviving EWAT appears to increase in mass to a small degree. The purpose of the present study was to determine the time course for fat pad mass and cellularity changes after EWATx and to test whether surviving EWAT adipocytes undergo hypertrophy or hyperplasia. Male Siberian hamsters underwent EWATx or sham EWATx (SHAM). At Week 0 and at 2-week intervals up to 12 weeks postsurgery, a representative sample of animals from each group were killed. EWAT, retroperitoneal WAT (RWAT), and inguinal WAT (IWAT) were removed, weighed, and processed for cellularity measurement. IWAT and, to a nonsignificant degree, RWAT, increased in mass after EWATx due to fat cell hypertrophy. These changes began as early as Week 4 postlipectomy, but no mass or cellularity change was significant until Week 12. The surviving EWAT adipocytes of EWATx hamsters also were larger than those of SHAM hamsters and, unlike EWAT adipocyte number, increased with time within the EWATx group. SHAM hamsters showed slight increases in the mass of EWAT, but not IWAT or RWAT, due to a nonsignificant doubling of EWAT adipocyte number during the 3 months of the experiment.

A role for testosterone in the maintenance of seasonally appropriate body mass but not in lipectomy-induced body fat compensation in Siberian hamsters.

The purpose of this study was to test whether serum testosterone (T) concentrations characteristic of reproductively active, long-day-housed Siberian hamsters are necessary for compensatory increases in nonexcised fat pads following removal of epididymal white adipose tissue (EWAT) and/or for the maintenance of seasonally appropriate body weights in these hamsters. Long-day-housed hamsters were castrated or left intact, sham or EWAT lipectomized, and given T or cholesterol (C) implants. All groups had ad libitum food access except for two castrated T-treated groups that were pair-fed to their C-treated counterparts to control for effects of T on food intake. C-treated castrates had decreased body weights compared with all other groups, suggesting a role of T in the maintenance of seasonally appropriate body mass. Since the T-treated hamsters pair-fed to these T-deficient animals exhibited seasonally appropriate body weights and fat pad masses, T does not appear to affect these parameters through the modulation of food intake. All fat pads of C-treated animals were smaller than those of ad libitum- or pair-fed, T-treated castrates; however, EWAT was the only fat pad that was smaller in the C-treated sham-lipectomized group than in gonad-intact sham-lipectomized hamsters. This result may indicate an enhanced sensitivity of EWAT to T. The effects of T on fat pad mass were not associated with proportionate changes in lipoprotein lipase activity, suggesting that the major effect of T on fat accumulation occurs through other mechanisms in this species. C-treated lipectomized hamsters compensated for the body fat deficit 8 weeks after lipectomy via statistically non-significant increases in retroperitoneal and inguinal WAT mass. This finding suggests that, whereas T is necessary for maintenance of seasonally-appropriate body weight, it is not necessary for fat pad compensation after EWAT lipectomy.

Body fat regulation after partial lipectomy in Siberian hamsters is photoperiod dependent and fat pad specific.

Siberian hamsters exhibit seasonal fluctuations in body weight (fat). Initial exposure to a short photoperiod results in body fat loss that reverses after approximately 22 wk of short-day exposure. The purpose of this study was to determine whether Siberian hamsters are able to recover body fat after surgical reduction of total lipid stores and if so, whether this ability is photoperiod dependent and fat pad specific. Either the largest pair of internal fat pads, the epididymal white adipose tissue (EWAT) or one pair of two large external depots, the inguinal (IWAT) fat pads, were removed from male hamsters housed for 22 wk in a long (LD) or short (SD) photoperiod. Retroperitoneal fat pad (RWAT) mass was increased in LD EWAT- and IWAT-lipectomized hamsters. IWAT mass also was increased in the LD EWAT-lipectomized hamsters. Neither SD-lipectomized group compensated for body fat loss in any of the measured fat pads. Increased food intake was not necessary for total body fat recovery, but undereating partially may be responsible for the lack of recovery in SDs. The results of these experiments demonstrate a photoperiod-dependent ability of male Siberian hamsters to regulate total body fat after partial lipectomy. In addition, recovery involves a fat pad-specific compensatory response to partial lipectomy, rather than a general increase in lipid deposition in all fat depots.

Photoperiod-dependent fat pad mass and cellularity changes after partial lipectomy in Siberian hamsters.

Long day (LD)-housed Siberian hamsters show compensatory mass increases in nonexcised white adipose tissue (WAT) after partial lipectomy, whereas hamsters exposed to short days (SDs) for 22 wk do not. The purpose of this experiment was to determine the cellularity changes underlying lipectomy-induced WAT compensation and whether the duration of SD exposure affects this compensation. Male Siberian hamsters were epididymal (E) or inguinal (I) WAT lipectomized (x) or sham-lipectomized (Sham) and either remained in LDs or were transferred to SDs and killed 6 or 12 wk later. In LDs, lipectomized hamsters showed compensatory mass increases in retroperitoneal WAT (RWAT) due to hyperplasia. IWAT mass also was increased by approximately 40% in LD-housed EWATx hamsters because of nonsignificant increases in adipocyte size and number at weeks 6 and 12, respectively. SD-housed hamsters responded to lipectomy by delaying the SD-associated body fat loss so that RWAT mass was reduced only one-third as much in lipectomized as in Sham hamsters, and the IWAT adipocytes of EWATx hamsters were larger than in Sham hamsters at week 6. At week 12, there was little indication of fat pad compensation by SD-housed hamsters. Collectively, the results of the present experiment and our previous study (16) suggest that the inhibitory effect of SDs on fat pad compensation after lipectomy increases with prolonged SD exposure.

Fat pad-specific compensatory mass increases after varying degrees of lipectomy in Siberian hamsters.

Long day-housed Siberian hamsters show compensatory mass increases in inguinal (I) white adipose tissue (WAT) after epididymal WAT pad (EWAT) removal (x) but do not increase EWAT mass after IWATx. This study tested whether EWAT is specifically unresponsive to IWATx or whether EWAT lacks responsiveness to body fat deficits in general. We also tested whether the compensatory mass increases that occur after side-specific body fat removal are unilateral or bilateral. Therefore EWAT and/or IWAT was removed unilaterally or bilaterally. The compensatory changes in WAT mass by the intact fat pads were measured 12 wk later. EWAT did not compensate for removal of its contralateral mate. Retroperitoneal WAT and IWAT showed greater compensatory mass increases ipsilateral to the side of fat pad removal when EWAT or IWAT pads were removed unilaterally but not after removal of larger amounts of body fat. These results suggest the following: 1) in general, the greater the lipectomy-induced lipid deficit, the greater is the relative fat pad mass compensation; 2) the restoration of body fat content after lipectomy may involve mechanisms that can detect the side of the lipid deficit and enhance fat deposition on this side; and 3) EWAT does not show compensatory mass increases after lipectomy.

Short-day-like body weight changes do not prevent fat pad compensation after lipectomy in Siberian hamsters.

Long-day (LD)-housed Siberian hamsters show compensatory increases in white adipose tissue (WAT) weight after lipectomy, whereas hamsters exposed to short days (SDs) for a long duration (22 wk) do not. We tested whether SD-induced body weight changes prevent fat pad compensation after lipectomy. In experiment 1, hamsters with lesions of the paraventricular nucleus of the hypothalamus (PVNx) rapidly increased body weight similarly to 22-wk SD-exposed hamsters. In experiment 2, LD-housed hamsters were food restricted for 22 wk and then pair fed with SD-housed hamsters for 12 wk to produce body weight changes mimicking those of ad libitum-fed SD-exposed animals. Epididymal WAT (EWAT) lipectomy (EWATx) of PVNx or food-restricted hamsters elicited compensatory increases in retroperitoneal and inguinal WAT (RWAT and IWAT) weights. Unlike other fat pads, EWAT was less affected by food restriction or PVNx than by SD exposure. In general, food restriction decreased adipocyte number, whereas SD exposure decreased adipocyte size. PVNx increased RWAT adipocyte size and IWAT adipocyte number. These results suggest that the lack of body fat compensation by EWATx hamsters exposed to SDs for a long duration is due to SD-associated responses other than body weight changes per se.

Factors related to success or failure of second renal transplants.

From January 1, 1968 to December 31, 1973, 50 patients received two or more kidney transplants. Patient and graft survival was highly dependent upon the source of the donor and to a lesser extent the functional duration of the first transplant and the elapsed time between first and second graft. Survival (patient and graft) was best in patients receiving two related grafts and worst in patients receiving two sequential cadaver grafts. Intermediate rates of success followed cadaver transplantation after rejection of a related graft. The highest failure rate was encountered when those patients who sustained an early loss of the first cadaver graft received a subsequent cadaver graft within a few months. We recommended removal of the acutely rejected graft and delay prior to retransplantation of patients who rapidly reject cadaver grafts in the face of maximal doses of immunosuppression. A delay will permit recovery from both the immunosuppression and any underlying subclinical infections, and will permit the recognition of anti-HL-A antibodies which may not be manifest soon after rejection. Retransplantation of the patient who is slowly rejecting the first kidney does not require prior removal of the rejected graft or delay in retransplantation.