Manipulation of Body Fat by Passive and Active Immunisation Against the Adipocyte

Futter, Clare Elisabeth (1988) Manipulation of Body Fat by Passive and Active Immunisation Against the Adipocyte. PhD thesis, University of Glasgow.

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The aim of the work described in this thesis was to devise a technique for the reduction of body fat by passive or active immunisation against the adipocyte. Passive immunisation of rats with an antiserum, raised in sheep, against rat adipocyte plasma membranes (A/S 83) caused a 50% reduction in parametrial adipocyte number which persisted, at least until 24 weeks after treatment. This was accompanied by a reduction in parametrial adipocyte size which persisted for 8 weeks but had recovered by 24 weeks, resulting in a 50% reduction in parametrial adipose mass at 24 weeks. Subcutaneous and peri-renal adipose depots were, initially, less affected and had recovered their total mass by 24 weeks after treatment. Differential effects on different adipose depots were found to be due largely to the site of injection of the antiserum. Body composition analysis showed that total body fat was reduced by 30% 8 weeks after treatment and lost fat was replaced by protein and water. Side effects of A/S 83 were limited to a reduction in food intake on the first day of treatment, which gradually recovered to reach normal levels by 4 days and transient proteinurea with fluctuations in body weight about 2 weeks after treatment in some rats. The initial effects of A/S 83 on adipose tissue and food intake were dependent on the presence of circulating complement. A doubling of serum free fatty acids and triglycerides occurred 6-24 h after treatment, then returned to normal levels by 48 h after treatment and was probably evidence of adipocyte destruction. Treatment with A/S 83 did not affect the ability of rats to undergo a normal pregnancy and lactation. More recent bleeds of the same sheep did not reproduce the in vivo effects of earlier bleeds of A/S 83 and so 2 additional antisera were raised against rat adipocyte plasma membranes. These new antisera, while reproducing the effects of A/S 83 on adipose tissue, had the additional side effects of anaesthetic-like effects immediately after administration and the production of gross liver abnormalities. The presence or absence of side effects could not be correlated with strength of binding to nervous tissue or hepatocyte plasma membranes, as determined by ELISA and Western blotting. An attempt was made to prepare rat adipocyte specific antigens by affinity purification of anti-(adipocyte plasma membrane) antibodies, adsorption of those antibodies with non-adipose tissues and the use of the adipocyte specific antibodies to affinity purify antigens from solubilized adipocyte plasma membranes. Six polypeptides, with molecular weights of 53-96 kD, were considerably enriched in the adipocyte specific antigen preparation. Antisera raised against the adipocyte specific antigens showed some binding to non-adipose tissues and antisera raised against hepatocyte and erythrocyte plasma membranes showed some binding to adipocyte specific antigens, which cast doubt on the true adipocyte specificity of some of the components of the adipocyte specific antigen preparation. However, the anti-(adipocyte specific antigen) antiserum showed considerably more adipocyte specificity than antisera raised against whole adipocyte plasma membranes, had fat-reducing properties in vivo and did not cause liver abnormalities. Adsorption of anti-(adipocyte plasma membrane) antisera with liver homogenate provided an antiserum that retained its effects on adipose tissue but no longer caused liver abnormalities. It is, therefore, likely that adipocyte specific antisera can have fat-reducing properties, but both the anti-(adipocyte specific antigen) antiserum and the adsorbed antiserum reproduced the anaesthetic-like effects of anti-(adipocyte plasma membrane) antisera and caused a reduction in food intake on the first day of treatment. Antisera raised against hepatocyte and erythrocyte plasma membranes had no effects on adipose tissue. Attempts were made to reproduce the effects of passive immunisation by means of active immunisation against the adipocyte, as this might prove a more practical approach for the treatment of large species. Rats were immunised with rat adipocyte plasma membranes or adipocyte specific antigens conjugated to BSA, or with BSA alone in complete Freunds adjuvant. Despite the absence of a convincing demonstration of circulating anti-(adipocyte plasma membrane) antibodies, adipocyte plasma membrane- and adipocyte specific antigen-treated rats showed a 40-50% reduction in adipocyte numbers and a compensatory increase in adipocyte size. In only 1 out of 3 groups of rats did active immunisation induce a reduction in adipose mass and, in this group, body weight was also reduced. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Physiology
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-77740
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53

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