Compounds researched for fat loss

[1] Visceral adipose tissue endpoint. In a randomised placebo-controlled trial in 412 patients with HIV and antiretroviral-associated abdominal fat accumulation, the primary endpoint of CT-measured visceral adipose tissue decreased by 15.2% with the GHRH analogue and increased by 5.0% with placebo over 26 weeks. Findings apply to that specific clinical population only.

[2] Pooled phase 3 analysis. A pooled analysis of two multicentre, double-blind, placebo-controlled phase 3 trials examined tesamorelin in HIV-infected patients with excess abdominal fat, reporting visceral adipose tissue outcomes alongside safety-extension data. The population studied was HIV-associated abdominal fat accumulation only.

[1] AMPK activation in rat muscle. In rat muscle preparations, AICA riboside was reported to increase AMP-activated protein kinase activity, fatty acid oxidation and glucose uptake. This is a foundational preclinical characterisation of AICAR as a pharmacological AMPK activator.

[2] Adipocyte lipolysis in vitro. In primary rat adipocytes, short-term AMPK activation by AICAR was reported to decrease lipolysis, with effects assessed at different glucose concentrations. Note the direction of that finding — it runs opposite to the assumption that an AMPK activator simply increases fat breakdown.

[1] Rodent adipose lipolytic activity. In obese Zucker rats, daily administration of AOD9604 was reported to reduce body-weight gain versus control over 19 days, with increased lipolytic activity measured in adipose tissue. Euglycaemic clamp measurements in the same animals showed no adverse effect on insulin sensitivity, unlike intact growth hormone.

[2] Fat oxidation in rodent obesity models. In obese mice, chronic administration of human growth hormone or a modified C-terminal growth hormone fragment was reported to increase fat oxidation and reduce body weight relative to control. This is a rodent model of diet-related obesity, not a human study.

[1] NNMT inhibition in adipocytes. In cultured adipocytes, membrane-permeable methylquinolinium NNMT inhibitors were reported to lower intracellular 1-methylnicotinamide, raise NAD+ and SAM, and suppress lipogenesis. In diet-induced obese mice, a potent inhibitor of this series reduced body weight and white adipose mass with no change in food intake.

[2] NNMT target validation. Antisense knockdown of nicotinamide N-methyltransferase in white adipose tissue and liver of diet-induced obese mice was reported to protect against diet-induced obesity. This target-validation work in mice underpins the later small-molecule NNMT inhibitor literature.

[1] Metabolism and insulin resistance. This research characterised the mitochondrial-derived peptide MOTS-c as a regulator of metabolic homeostasis, reporting effects on insulin sensitivity in laboratory models.

[2] Exercise and muscle homeostasis. This paper reports two distinct things that should not be merged: endogenous MOTS-c rose with exercise in human subjects, while ADMINISTERED MOTS-c affected physical capacity in mice. The mouse arm is the interventional result; the human arm is observational.

[1] Adipose vasculature targeting in mice. In mouse research, a peptide motif (CKGGRAKDC) was reported to home to white fat vasculature and to associate with prohibitin, identifying prohibitin as a vascular marker of adipose tissue. Coupling a proapoptotic peptide to that motif produced targeted ablation of adipose tissue in the animals studied.

[2] Non-human primate research. In obese Old World monkeys, the ligand-directed peptidomimetic termed adipotide was reported to induce apoptosis within blood vessels of white adipose tissue, with associated weight loss and changes in insulin resistance. The same study also reported reversible renal proximal-tubule changes in the treated animals — a finding that belongs alongside the efficacy result. These are preclinical primate data and were not followed by human trials.